rs146630359

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6BP7BS2_Supporting

The NM_000341.4(SLC3A1):c.231T>A(p.Ser77Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,614,254 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 11 hom. )

Consequence

SLC3A1
NM_000341.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -4.31

Publications

6 publications found

Variant links:

Genes affected

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SLC3A1 Gene-Disease associations (from GenCC):

cystinuria
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
cystinuria type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC3A1 links:

ENSG00000285542 (HGNC:):

ENSG00000285542 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-44275766-T-A is Benign according to our data. Variant chr2-44275766-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 526034.

BP7

Synonymous conserved (PhyloP=-4.31 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A1	NM_000341.4 link	c.231T>A	p.Ser77Ser	synonymous_variant	Exon 1 of 10	ENST00000260649.11	NP_000332.2	Q07837-1A0A0S2Z4E1
SLC3A1	XM_011533047.4 link	c.231T>A	p.Ser77Ser	synonymous_variant	Exon 1 of 10		XP_011531349.1	B8ZZK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC3A1	ENST00000260649.11 link	c.231T>A	p.Ser77Ser	synonymous_variant	Exon 1 of 10	1	NM_000341.4	ENSP00000260649.6	Q07837-1
ENSG00000285542	ENST00000649044.1 link	n.*242T>A		non_coding_transcript_exon_variant	Exon 6 of 15			ENSP00000497083.1	A0A3B3IS24
ENSG00000285542	ENST00000649044.1 link	n.*242T>A		3_prime_UTR_variant	Exon 6 of 15			ENSP00000497083.1	A0A3B3IS24

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00256

AC:

643

AN:

251402

AF XY:

0.00274

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.00436

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00335

AC:

4904

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

2369

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.000984

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00559

AC:

146

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000371

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00148

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00395

AC:

4396

AN:

1112010

Other (OTH)

AF:

0.00300

AC:

181

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

311

622

933

1244

1555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.00247

AC:

377

AN:

152362

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000721

AC:

AN:

41594

American (AMR)

AF:

0.00346

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00363

AC:

247

AN:

68032

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00323

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00403

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC3A1: BP4, BP7 -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cystinuria

Uncertain:1Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

-0.86

CADD

Benign

0.039

(source)

DANN

Benign

0.80

PhyloP100

-4.3

PromoterAI

0.0058

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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