chr22-32043317-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000343.4(SLC5A1):c.36G>A(p.Ala12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,614,080 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A12A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )
Consequence
SLC5A1
NM_000343.4 synonymous
NM_000343.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0540
Genes affected
SLC5A1 (HGNC:11036): (solute carrier family 5 member 1) This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 22-32043317-G-A is Benign according to our data. Variant chr22-32043317-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 903161.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=0.054 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| SLC5A1 | NM_000343.4 | c.36G>A | p.Ala12= | synonymous_variant | 1/15 | ENST00000266088.9 | |
| SLC5A1 | XM_011530331.2 | c.36G>A | p.Ala12= | synonymous_variant | 1/12 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC5A1 | ENST00000266088.9 | c.36G>A | p.Ala12= | synonymous_variant | 1/15 | 1 | NM_000343.4 | P1 |
Frequencies
GnomAD3 genomes 0.000125 AC: 19AN: 152256Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000199 AC: 50AN: 250760Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135628
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GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 66AN XY: 727218
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GnomAD4 genome 0.000125 AC: 19AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74380
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Congenital glucose-galactose malabsorption Uncertain:1Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
SLC5A1-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 10, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at