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GeneBe

2-27201806-GA-G

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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.09
Variant links:
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
SLC5A6NM_021095.4 linkuse as main transcriptc.1403del p.Phe468SerfsTer9 frameshift_variant 14/17 ENST00000310574.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC5A6ENST00000310574.8 linkuse as main transcriptc.1403del p.Phe468SerfsTer9 frameshift_variant 14/171 NM_021095.4 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
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 submitterclinical testingIllumina Laboratory Services, IlluminaAug 02, 2023The 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27424674; API