rs698761
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000341.4(SLC3A1):c.1854G>A(p.Met618Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,613,640 control chromosomes in the GnomAD database, including 349,250 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000341.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC3A1 | NM_000341.4 | c.1854G>A | p.Met618Ile | missense_variant | 10/10 | ENST00000260649.11 | |
PREPL | NM_001171613.2 | c.*921C>T | 3_prime_UTR_variant | 14/14 | ENST00000409411.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC3A1 | ENST00000260649.11 | c.1854G>A | p.Met618Ile | missense_variant | 10/10 | 1 | NM_000341.4 | P1 | |
PREPL | ENST00000409411.6 | c.*921C>T | 3_prime_UTR_variant | 14/14 | 1 | NM_001171613.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.535 AC: 81262AN: 151978Hom.: 24260 Cov.: 33
GnomAD3 exomes AF: 0.594 AC: 148070AN: 249352Hom.: 46493 AF XY: 0.609 AC XY: 82177AN XY: 134918
GnomAD4 exome AF: 0.660 AC: 964425AN: 1461544Hom.: 324999 Cov.: 50 AF XY: 0.662 AC XY: 481119AN XY: 727116
GnomAD4 genome ? AF: 0.534 AC: 81251AN: 152096Hom.: 24251 Cov.: 33 AF XY: 0.529 AC XY: 39348AN XY: 74330
ClinVar
Submissions by phenotype
Cystinuria Pathogenic:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Pathogenic, criteria provided, single submitter | research | Biotechnology Lab, University of Central Punjab | Feb 10, 2023 | A molecular and computational study performed on the Pakistani population reported this missense variant (M618I) in the SLC3A1 gene, as a pathogenic variant, by using the technique of Next-generation sequencing. The variant was potentially involved in causing Cystinuria by altering the structural and functional effect of the rBAT protein coded by the SLC3A1 gene. The variant was confirmed by ARMS-PCR at the population level (Zafar & Awais, 2023). - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at