chr10-13319210-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP5_Moderate
The NM_012247.5(SEPHS1):c.1111C>T(p.Arg371Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R371G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_012247.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPHS1 | NM_012247.5 | c.1111C>T | p.Arg371Trp | missense_variant | 9/9 | ENST00000327347.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPHS1 | ENST00000327347.10 | c.1111C>T | p.Arg371Trp | missense_variant | 9/9 | 1 | NM_012247.5 | P1 | |
SEPHS1 | ENST00000545675.5 | c.910C>T | p.Arg304Trp | missense_variant | 8/8 | 1 | |||
SEPHS1 | ENST00000378614.8 | c.898C>T | p.Arg300Trp | missense_variant | 8/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152170Hom.: 0 Cov.: 33 FAILED QC
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
SEPHS1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Undiagnosed Diseases Network, NIH | Dec 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.