rs796262035

Positions:

• chr2-44301128-GT-G
• chr2-44301128-GT-GTT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_Strong BP6_Very_Strong BA1

The ENST00000410056.7(SLC3A1):​c.1139delT​(p.Leu380fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,613,908 control chromosomes in the GnomAD database, including 9,573 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L380L) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.14 (1770 hom., cov: 30)
  • Exomes 𝑓: 0.096 (7803 hom.)
• Consequence: SLC3A1 ENST00000410056.7 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00

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]

ENSG00000285542 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 17 pathogenic variants in the truncated region.
• BP6: Variant 2-44301128-GT-G is Benign according to our data. Variant chr2-44301128-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 336199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-44301128-GT-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A1	NM_000341.4	c.1136+3delT		splice_region_variant, intron_variant		ENST00000260649.11	NP_000332.2
SLC3A1	XM_011533047.4	c.1136+3delT		splice_region_variant, intron_variant			XP_011531349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC3A1	ENST00000260649.11	c.1136+3delT		splice_region_variant, intron_variant		1	NM_000341.4	ENSP00000260649.6
ENSG00000285542	ENST00000649044.1	n.*1147+3delT		splice_region_variant, intron_variant				ENSP00000497083.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20672 AN: 152022 Hom.: 1763 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.0875 AC: 21977 AN: 251244 Hom.: 1336 AF XY: 0.0830 AC XY: 11268 AN XY: 135822

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.0597

Gnomad ASJ exome AF: 0.0849

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0206

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0903

GnomAD4 exome AF: 0.0962 AC: 140568 AN: 1461768 Hom.: 7803 Cov.: 30 AF XY: 0.0936 AC XY: 68053 AN XY: 727188

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.0840

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.0990

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0997

GnomAD4 genome AF: 0.136 AC: 20715 AN: 152140 Hom.: 1770 Cov.: 30 AF XY: 0.134 AC XY: 9944 AN XY: 74374

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0858

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0334 Hom.: 219

Bravo AF: 0.142

Asia WGS AF: 0.0300 AC: 105 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystinuria Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 242/2178=11.1% -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs796262035; hg19: chr2-44528267;