rs387907276

chr2-44313931-T-Achr2-44313931-T-Cchr2-44313931-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000341.4(SLC3A1):c.1597T>A(p.Tyr533Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.18

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942
• PP5: Variant 2-44313931-T-A is Pathogenic according to our data. Variant chr2-44313931-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 37080.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A1	NM_000341.4	c.1597T>A	p.Tyr533Asn	missense_variant	9/10	ENST00000260649.11
SLC3A1	XM_011533047.4	c.1597T>A	p.Tyr533Asn	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A1	ENST00000260649.11	c.1597T>A	p.Tyr533Asn	missense_variant	9/10	1	NM_000341.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cystinuria Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.16	T;D;T;.;.;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
Sift4G	Uncertain	0.048	D;D;D;T;T;D;D
Polyphen		1.0, 1.0	.;D;D;.;.;.;.
Vest4		0.98
MutPred		0.65		Gain of disorder (P = 0.0066);Gain of disorder (P = 0.0066);Gain of disorder (P = 0.0066);Gain of disorder (P = 0.0066);.;.;.;
MVP		0.99
MPC		0.028
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs387907276; hg19: chr2-44541070;