rs2631365

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003060.4(SLC22A5):c.285T>C(p.Leu95Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,582,580 control chromosomes in the GnomAD database, including 135,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L95L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.41 ( 13132 hom., cov: 33)

Exomes 𝑓: 0.40 ( 121958 hom. )

Consequence

SLC22A5
NM_003060.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.298

Publications

28 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 links:

MIR3936HG (HGNC:40538): (MIR3936 host gene)

MIR3936HG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-132370257-T-C is Benign according to our data. Variant chr5-132370257-T-C is described in ClinVar as Benign. ClinVar VariationId is 94099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.298 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4 link	c.285T>C	p.Leu95Leu	synonymous_variant	Exon 1 of 10	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.285T>C	p.Leu95Leu	synonymous_variant	Exon 1 of 10	1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61787

AN:

151952

Hom.:

13124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.392

GnomAD2 exomes

AF:

0.433

AC:

82365

AN:

190330

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.405

AC:

579057

AN:

1430510

Hom.:

121958

Cov.:

AF XY:

0.412

AC XY:

292033

AN XY:

708786

show subpopulations

African (AFR)

AF:

0.353

AC:

11583

AN:

32772

American (AMR)

AF:

0.324

AC:

12792

AN:

39448

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10270

AN:

25682

East Asian (EAS)

AF:

0.668

AC:

25247

AN:

37786

South Asian (SAS)

AF:

0.620

AC:

51246

AN:

82710

European-Finnish (FIN)

AF:

0.505

AC:

25053

AN:

49598

Middle Eastern (MID)

AF:

0.471

AC:

2689

AN:

5712

European-Non Finnish (NFE)

AF:

0.379

AC:

415559

AN:

1097512

Other (OTH)

AF:

0.415

AC:

24618

AN:

59290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

20206

40411

60617

80822

101028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13238

26476

39714

52952

66190

<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:

0.407

AC:

61825

AN:

152070

Hom.:

13132

Cov.:

AF XY:

0.417

AC XY:

31020

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.359

AC:

14913

AN:

41514

American (AMR)

AF:

0.352

AC:

5389

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1444

AN:

3468

East Asian (EAS)

AF:

0.668

AC:

3440

AN:

5146

South Asian (SAS)

AF:

0.642

AC:

3092

AN:

4816

European-Finnish (FIN)

AF:

0.512

AC:

5419

AN:

10588

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26945

AN:

67924

Other (OTH)

AF:

0.392

AC:

829

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1894

3787

5681

7574

9468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.366

Hom.:

4306

Bravo

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal carnitine transport defect

Benign:7

Aug 01, 2017

Phosphorus, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 variant was observed in the general population by the ExAC project at an allele frequency of ~50% across diverse ethnicities including numerous homozygotes indicating the variant to be a neutral polymorphism. Therefore the variant is classified as Benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.6

(source)

DANN

Benign

0.74

PhyloP100

-0.30

PromoterAI

0.0037

Neutral

(source)

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