Variant 2-44275569-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000341.4(SLC3A1):c.34G>A(p.Glu12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SLC3A1
NM_000341.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

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:

ENSG00000285542 (HGNC:):

ENSG00000285542 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014664054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A1	NM_000341.4 link	c.34G>A	p.Glu12Lys	missense_variant	1/10	ENST00000260649.11	NP_000332.2	Q07837-1A0A0S2Z4E1
SLC3A1	XM_011533047.4 link	c.34G>A	p.Glu12Lys	missense_variant	1/10		XP_011531349.1	B8ZZK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC3A1	ENST00000260649.11 link	c.34G>A	p.Glu12Lys	missense_variant	1/10	1	NM_000341.4	ENSP00000260649.6	Q07837-1
ENSG00000285542	ENST00000649044.1 link	n.*45G>A		non_coding_transcript_exon_variant	6/15			ENSP00000497083.1	A0A3B3IS24
ENSG00000285542	ENST00000649044.1 link	n.*45G>A		3_prime_UTR_variant	6/15			ENSP00000497083.1	A0A3B3IS24

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251306

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135832

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:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727228

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:

0.000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cystinuria

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.10

DANN

Benign

0.84

DEOGEN2

Benign

0.012

T;T;T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.54

T;T;T;T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.015

T;T;T;T;T;T

MetaSVM

Pathogenic

0.94

MutationAssessor

Benign

-0.13

.;N;.;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.36

.;N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.55

.;T;T;T;T;T

Sift4G

Benign

0.74

T;T;T;T;T;T

Polyphen

0.0020, 0.0040

.;B;B;.;.;.

Vest4

0.15

MutPred

0.31

Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);

MVP

0.78

MPC

0.0061

ClinPred

0.015

GERP RS

-6.1

Varity_R

0.026

gMVP

0.33

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