15-90219793-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000411539.7(SEMA4B):c.385C>T(p.Arg129Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,612,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000411539.7 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEMA4B | NM_198925.4 | c.385C>T | p.Arg129Cys | missense_variant, splice_region_variant | 4/14 | ENST00000411539.7 | NP_945119.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEMA4B | ENST00000411539.7 | c.385C>T | p.Arg129Cys | missense_variant, splice_region_variant | 4/14 | 1 | NM_198925.4 | ENSP00000394720 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000444 AC: 11AN: 247546Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134322
GnomAD4 exome AF: 0.000134 AC: 195AN: 1459822Hom.: 0 Cov.: 30 AF XY: 0.000138 AC XY: 100AN XY: 726220
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.385C>T (p.R129C) alteration is located in exon 5 (coding exon 4) of the SEMA4B gene. This alteration results from a C to T substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at