rs121912694

chr2-44280827-G-Achr2-44280827-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_Strong PP5

The NM_000341.4(SLC3A1):c.542G>A(p.Arg181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SLC3A1 NM_000341.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.552

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 Uncertain_significance. Variant got 5 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947
• PP5: Variant 2-44280827-G-A is Pathogenic according to our data. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A1	NM_000341.4	c.542G>A	p.Arg181Gln	missense_variant	2/10	ENST00000260649.11
SLC3A1	XM_011533047.4	c.542G>A	p.Arg181Gln	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A1	ENST00000260649.11	c.542G>A	p.Arg181Gln	missense_variant	2/10	1	NM_000341.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251424 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727152

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

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

Apr 01, 1994

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Uncertain	0.060
Cadd	Benign	10
Dann	Benign	0.93
DEOGEN2	Benign	0.014	T;D;T;.;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D
MetaSVM	Pathogenic	0.87	D
MutationTaster	Benign	0.058	A;A;A;A;A
PrimateAI	Benign	0.18	T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.21, 0.17	.;B;B;.;.;.
Vest4		0.67
MutPred		0.87		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		0.88
MPC		0.0065
ClinPred		0.074	T
GERP RS		0.41
Varity_R		0.096
gMVP		0.60

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: rs121912694; hg19: chr2-44507966;