Variant 2-44280827-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM5PP3_Moderate

The ENST00000260649.11(SLC3A1):c.542G>T(p.Arg181Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R181Q) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLC3A1
ENST00000260649.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.552

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 Uncertain_significance. Variant got 4 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-44280827-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 18118.Status of the report is no_assertion_criteria_provided, 0 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A1	NM_000341.4 linkuse as main transcript	c.542G>T	p.Arg181Leu	missense_variant	2/10	ENST00000260649.11	NP_000332.2
SLC3A1	XM_011533047.4 linkuse as main transcript	c.542G>T	p.Arg181Leu	missense_variant	2/10		XP_011531349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC3A1	ENST00000260649.11 linkuse as main transcript	c.542G>T	p.Arg181Leu	missense_variant	2/10	1	NM_000341.4	ENSP00000260649	P1	Q07837-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251424

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000277

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

8.6

DANN

Benign

0.35

DEOGEN2

Benign

0.024

T;D;T;.;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.88

D;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D

MetaSVM

Pathogenic

0.80

MutationAssessor

Benign

1.7

.;L;.;L;L;L

MutationTaster

Benign

0.70

N;N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.9

.;N;N;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

0.56

.;T;T;T;T;T

Sift4G

Benign

0.64

T;T;T;T;T;T

Polyphen

0.44, 0.59

.;B;P;.;.;.

Vest4

0.63

MutPred

0.79

Loss of methylation at R181 (P = 0.0916);Loss of methylation at R181 (P = 0.0916);Loss of methylation at R181 (P = 0.0916);Loss of methylation at R181 (P = 0.0916);Loss of methylation at R181 (P = 0.0916);Loss of methylation at R181 (P = 0.0916);

MVP

0.70

MPC

0.0070

ClinPred

0.084

GERP RS

0.41

Varity_R

0.18

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over