rs121912695

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_StrongPP5

The ENST00000260649.11(SLC3A1):ā€‹c.1955C>Gā€‹(p.Thr652Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,730 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T652A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

SLC3A1
ENST00000260649.11 missense

Scores

5
2
12

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.533
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]
PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.964
PP5
Variant 2-44320536-C-G is Pathogenic according to our data. Variant chr2-44320536-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 18119.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC3A1NM_000341.4 linkuse as main transcriptc.1955C>G p.Thr652Arg missense_variant 10/10 ENST00000260649.11 NP_000332.2
PREPLNM_001171613.2 linkuse as main transcriptc.*820G>C 3_prime_UTR_variant 14/14 ENST00000409411.6 NP_001165084.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC3A1ENST00000260649.11 linkuse as main transcriptc.1955C>G p.Thr652Arg missense_variant 10/101 NM_000341.4 ENSP00000260649 P1Q07837-1
PREPLENST00000409411.6 linkuse as main transcriptc.*820G>C 3_prime_UTR_variant 14/141 NM_001171613.2 ENSP00000387095 P4Q4J6C6-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461730
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727172
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:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Cystinuria Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 1994- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.28
T;.;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.59
T;T;T
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Benign
1.7
L;.;.
MutationTaster
Benign
0.0061
A;A;A;A;A;A;A
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Uncertain
0.64
Sift
Benign
0.037
D;D;D
Sift4G
Uncertain
0.056
T;T;T
Polyphen
0.061
B;.;.
Vest4
0.26
MutPred
0.81
Loss of catalytic residue at T652 (P = 0.0393);.;.;
MVP
0.87
MPC
0.0083
ClinPred
0.38
T
GERP RS
0.22
Varity_R
0.30
gMVP
0.86

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.

Other links and lift over

dbSNP: rs121912695; hg19: chr2-44547675; API