5-132369766-C-G

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.-207C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 592,348 control chromosomes in the GnomAD database, including 110,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27799 hom., cov: 33)

Exomes 𝑓: 0.60 ( 82696 hom. )

Consequence

SLC22A5
NM_003060.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.35

Publications

106 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:

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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=-0.81).

BP6

Variant 5-132369766-C-G is Benign according to our data. Variant chr5-132369766-C-G is described in ClinVar as [Benign]. Clinvar id is 350806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4 link	c.-207C>G		5_prime_UTR_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.-207C>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90534

AN:

151872

Hom.:

27771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.554

GnomAD4 exome

AF:

0.596

AC:

262284

AN:

440368

Hom.:

82696

Cov.:

AF XY:

0.605

AC XY:

138440

AN XY:

228810

show subpopulations

African (AFR)

AF:

0.607

AC:

5312

AN:

8746

American (AMR)

AF:

0.673

AC:

6432

AN:

9564

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

5591

AN:

11622

East Asian (EAS)

AF:

0.999

AC:

25012

AN:

25036

South Asian (SAS)

AF:

0.857

AC:

29454

AN:

34372

European-Finnish (FIN)

AF:

0.662

AC:

18780

AN:

28356

Middle Eastern (MID)

AF:

0.568

AC:

1055

AN:

1858

European-Non Finnish (NFE)

AF:

0.528

AC:

156492

AN:

296430

Other (OTH)

AF:

0.581

AC:

14156

AN:

24384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

4897

9793

14690

19586

24483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.596

AC:

90608

AN:

151980

Hom.:

27799

Cov.:

AF XY:

0.610

AC XY:

45362

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.605

AC:

25094

AN:

41472

American (AMR)

AF:

0.615

AC:

9402

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1716

AN:

3472

East Asian (EAS)

AF:

0.997

AC:

5129

AN:

5144

South Asian (SAS)

AF:

0.872

AC:

4213

AN:

4832

European-Finnish (FIN)

AF:

0.665

AC:

7015

AN:

10546

Middle Eastern (MID)

AF:

0.558

AC:

163

AN:

292

European-Non Finnish (NFE)

AF:

0.536

AC:

36398

AN:

67926

Other (OTH)

AF:

0.559

AC:

1179

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1907

3814

5722

7629

9536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.581

Hom.:

3213

Bravo

AF:

0.587

Asia WGS

AF:

0.908

AC:

3144

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal carnitine transport defect

Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23127916, 16931768, 15107849, 19141711, 22325173, 21279723, 16255050) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.3

PromoterAI

0.55

Over-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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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5-132369766-C-G

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