rs606231301
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_003051.4(SLC16A1):c.499del(p.Val167PhefsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,454,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SLC16A1
NM_003051.4 frameshift
NM_003051.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.43
Genes affected
SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-112917906-AC-A is Pathogenic according to our data. Variant chr1-112917906-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 158083.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A1 | NM_003051.4 | c.499del | p.Val167PhefsTer13 | frameshift_variant | 4/5 | ENST00000369626.8 | |
SLC16A1 | NM_001166496.2 | c.499del | p.Val167PhefsTer13 | frameshift_variant | 4/5 | ||
SLC16A1 | XM_047428789.1 | c.499del | p.Val167PhefsTer13 | frameshift_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A1 | ENST00000369626.8 | c.499del | p.Val167PhefsTer13 | frameshift_variant | 4/5 | 1 | NM_003051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244676Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132364
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GnomAD4 exome AF: 0.00000412 AC: 6AN: 1454742Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723282
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Monocarboxylate transporter 1 deficiency, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 13, 2014 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2022 | Identified as heterozygous in a child with multiple episodes of ketotic hypoglycemia, ketoacidosis, and ketonuria in published literature (van Hasselt et al., 2014); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25390740) - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at