chr2-27201806-GA-G
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_021095.4(SLC5A6):c.1403del(p.Phe468SerfsTer9) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
SLC5A6
NM_021095.4 frameshift
NM_021095.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.09
Genes affected
SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-27201806-GA-G is Pathogenic according to our data. Variant chr2-27201806-GA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2627917.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A6 | NM_021095.4 | c.1403del | p.Phe468SerfsTer9 | frameshift_variant | 14/17 | ENST00000310574.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A6 | ENST00000310574.8 | c.1403del | p.Phe468SerfsTer9 | frameshift_variant | 14/17 | 1 | NM_021095.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodegeneration, infantile-onset, biotin-responsive Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Aug 02, 2023 | The SLC5A6 c.1403del (p.Phe468SerfsTer9) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.1403del (p.Phe468SerfsTer9) variant is classified as likely pathogenic for SLC5A6-related multivitamin-dependent neurometabolic disorder. - |
Computational scores
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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
Publications
No publications associated with this variant yet.