rs12471298
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1
The NM_017789.5(SEMA4C):c.2077G>T(p.Glu693Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,612,808 control chromosomes in the GnomAD database, including 1,114 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.012 ( 126 hom., cov: 33)
Exomes 𝑓: 0.0065 ( 988 hom. )
Consequence
SEMA4C
NM_017789.5 stop_gained
NM_017789.5 stop_gained
Scores
3
3
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.28
Genes affected
SEMA4C (HGNC:10731): (semaphorin 4C) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.17 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA4C | NM_017789.5 | c.2077G>T | p.Glu693Ter | stop_gained | 15/15 | ENST00000305476.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA4C | ENST00000305476.10 | c.2077G>T | p.Glu693Ter | stop_gained | 15/15 | 1 | NM_017789.5 | P1 | |
SEMA4C | ENST00000467747.1 | n.2068G>T | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
SEMA4C | ENST00000474420.1 | n.1310G>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
SEMA4C | ENST00000482925.5 | n.2467G>T | non_coding_transcript_exon_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1756AN: 152182Hom.: 123 Cov.: 33
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GnomAD3 exomes AF: 0.0298 AC: 7393AN: 248396Hom.: 815 AF XY: 0.0217 AC XY: 2937AN XY: 135090
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GnomAD4 exome AF: 0.00645 AC: 9426AN: 1460508Hom.: 988 Cov.: 31 AF XY: 0.00530 AC XY: 3853AN XY: 726544
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GnomAD4 genome ? AF: 0.0116 AC: 1770AN: 152300Hom.: 126 Cov.: 33 AF XY: 0.0121 AC XY: 898AN XY: 74478
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Not reported inComputational scores
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Name
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Prediction
BayesDel_addAF
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D
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MutationTaster
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Vest4
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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