2-44275649-A-C

Position:

chr2-44275649-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000260649.11(SLC3A1):c.114A>C(p.Gly38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,613,626 control chromosomes in the GnomAD database, including 480,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43627 hom., cov: 33)

Exomes 𝑓: 0.77 ( 436813 hom. )

Consequence

SLC3A1
ENST00000260649.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0880

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 2-44275649-A-C is Benign according to our data. Variant chr2-44275649-A-C is described in ClinVar as [Benign]. Clinvar id is 336184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-44275649-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.088 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A1	NM_000341.4 linkuse as main transcript	c.114A>C	p.Gly38=	synonymous_variant	1/10	ENST00000260649.11	NP_000332.2
SLC3A1	XM_011533047.4 linkuse as main transcript	c.114A>C	p.Gly38=	synonymous_variant	1/10		XP_011531349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC3A1	ENST00000260649.11 linkuse as main transcript	c.114A>C	p.Gly38=	synonymous_variant	1/10	1	NM_000341.4	ENSP00000260649	P1	Q07837-1

Frequencies

GnomAD3 genomes

AF:

0.752

AC:

114387

AN:

152090

Hom.:

43579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.795

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.799

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.838

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.775

Gnomad OTH

AF:

0.749

GnomAD3 exomes

AF:

0.723

AC:

181054

AN:

250552

Hom.:

67633

AF XY:

0.735

AC XY:

99502

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.789

Gnomad EAS exome

AF:

0.355

Gnomad SAS exome

AF:

0.854

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.776

Gnomad OTH exome

AF:

0.745

GnomAD4 exome

AF:

0.769

AC:

1123652

AN:

1461418

Hom.:

436813

Cov.:

AF XY:

0.772

AC XY:

560974

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.802

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.854

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.785

Gnomad4 OTH exome

AF:

0.760

GnomAD4 genome

AF:

0.752

AC:

114494

AN:

152208

Hom.:

43627

Cov.:

AF XY:

0.746

AC XY:

55476

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.796

Gnomad4 AMR

AF:

0.688

Gnomad4 ASJ

AF:

0.799

Gnomad4 EAS

AF:

0.355

Gnomad4 SAS

AF:

0.839

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.775

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.770

Hom.:

91592

Bravo

AF:

0.747

Asia WGS

AF:

0.642

AC:

2236

AN:

3478

EpiCase

AF:

0.786

EpiControl

AF:

0.782

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystinuria

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	research	Biotechnology Lab, University of Central Punjab	Feb 10, 2023	A molecular and computational study performed on the Pakistani population reported this synonymous variant (G38=) in the SLC3A1 gene, as a benign variant, by using the technique of Next-generation sequencing. This variant might be the reason for causing the disease or increasing the severity of the already inherited Cystinuria. The variant was confirmed by ARMS-PCR at the population level (Zafar & Awais, 2023). -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

DANN

Benign

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over