rs606231299
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_003051.4(SLC16A1):c.937C>T(p.Arg313*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 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 (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC16A1
NM_003051.4 stop_gained
NM_003051.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 2.07
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 Pathogenic. Variant got 14 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. Fraction of 0.377 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-112917469-G-A is Pathogenic according to our data. Variant chr1-112917469-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 158079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC16A1 | NM_003051.4 | c.937C>T | p.Arg313* | stop_gained | 4/5 | ENST00000369626.8 | NP_003042.3 | |
SLC16A1 | NM_001166496.2 | c.937C>T | p.Arg313* | stop_gained | 4/5 | NP_001159968.1 | ||
SLC16A1 | XM_047428789.1 | c.937C>T | p.Arg313* | stop_gained | 4/5 | XP_047284745.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC16A1 | ENST00000369626.8 | c.937C>T | p.Arg313* | stop_gained | 4/5 | 1 | NM_003051.4 | ENSP00000358640.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251304Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135838
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727230
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 13, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense 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; This variant is associated with the following publications: (PMID: 35729663, 25390740) - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | This sequence change creates a premature translational stop signal (p.Arg313*) in the SLC16A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC16A1 are known to be pathogenic (PMID: 25390740). This variant is present in population databases (rs606231299, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive SLC16A1-related conditions (PMID: 25390740). ClinVar contains an entry for this variant (Variation ID: 158079). For these reasons, this variant has been classified as Pathogenic. - |
Ketoacidosis due to monocarboxylate transporter-1 deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Sep 01, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 25390740). The variant has been reported to be associated with SLC16A1-related disorder (ClinVar ID: VCV000158079 / PMID: 25390740). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, criteria provided, single submitter | clinical testing | Pediatric/Medical Genetics, Ministry of Health, Qatif Central Hospital | - | - - |
Monocarboxylate transporter 1 deficiency, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 13, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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