5-132385512-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003060.4(SLC22A5):c.824+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,609,746 control chromosomes in the GnomAD database, including 137,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13078 hom., cov: 33)

Exomes 𝑓: 0.40 ( 124506 hom. )

Consequence

SLC22A5
NM_003060.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.144

Publications

45 publications found

Variant links:

Genes affected

SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SLC22A5 Gene-Disease associations (from GenCC):

systemic primary carnitine deficiency disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
short QT syndrome
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

SLC22A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-132385512-T-C is Benign according to our data. Variant chr5-132385512-T-C is described in ClinVar as Benign. ClinVar VariationId is 94102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4 link	c.824+13T>C		intron_variant	Intron 4 of 9	ENST00000245407.8	NP_003051.1	O76082-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8 link	c.824+13T>C		intron_variant	Intron 4 of 9	1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61669

AN:

151988

Hom.:

13070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.435

AC:

109129

AN:

250752

AF XY:

0.448

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.508

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.404

AC:

589082

AN:

1457640

Hom.:

124506

Cov.:

AF XY:

0.412

AC XY:

298653

AN XY:

725370

show subpopulations

African (AFR)

AF:

0.354

AC:

11818

AN:

33416

American (AMR)

AF:

0.325

AC:

14515

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10456

AN:

26112

East Asian (EAS)

AF:

0.668

AC:

26484

AN:

39648

South Asian (SAS)

AF:

0.621

AC:

53497

AN:

86164

European-Finnish (FIN)

AF:

0.505

AC:

26940

AN:

53348

Middle Eastern (MID)

AF:

0.471

AC:

2708

AN:

5752

European-Non Finnish (NFE)

AF:

0.377

AC:

417593

AN:

1108234

Other (OTH)

AF:

0.416

AC:

25071

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

16272

32545

48817

65090

81362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13236

26472

39708

52944

66180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.406

AC:

61709

AN:

152106

Hom.:

13078

Cov.:

AF XY:

0.417

AC XY:

30994

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.359

AC:

14901

AN:

41498

American (AMR)

AF:

0.352

AC:

5373

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3470

East Asian (EAS)

AF:

0.670

AC:

3462

AN:

5168

South Asian (SAS)

AF:

0.641

AC:

3095

AN:

4826

European-Finnish (FIN)

AF:

0.511

AC:

5398

AN:

10566

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.395

AC:

26853

AN:

67980

Other (OTH)

AF:

0.391

AC:

828

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1859

3717

5576

7434

9293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.389

Hom.:

20278

Bravo

AF:

0.385

Asia WGS

AF:

0.617

AC:

2145

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal carnitine transport defect

Benign:5

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 20, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 07, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Apr 18, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary:The c.824+13T>C in SLC22A5 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 44%, including numerous homozygous occurrences. The observed frequency exceeds the maximum expected allele frequency for a pathogenic SLC22A variant, suggesting that it is a common polymorphism. In addition, the variant has been reported as Benign/Polymorphism by reputable database/clinical laboratory and published reports (Tang et al., 2002). Taken together, this variant has been classified as Benign. -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

(source)

DANN

Benign

0.43

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over