2-96860903-G-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_017789.5(SEMA4C):āc.2225C>Gā(p.Ser742Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,460,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000016 ( 0 hom. )
Consequence
SEMA4C
NM_017789.5 missense
NM_017789.5 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 3.37
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 -3 ACMG points.
PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SEM4C_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.40050715).
BS2
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEMA4C | NM_017789.5 | c.2225C>G | p.Ser742Cys | missense_variant | 15/15 | ENST00000305476.10 | NP_060259.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEMA4C | ENST00000305476.10 | c.2225C>G | p.Ser742Cys | missense_variant | 15/15 | 1 | NM_017789.5 | ENSP00000306844.5 | ||
SEMA4C | ENST00000467747.1 | n.2216C>G | non_coding_transcript_exon_variant | 3/3 | 2 | |||||
SEMA4C | ENST00000474420.1 | n.1458C>G | non_coding_transcript_exon_variant | 2/2 | 2 | |||||
SEMA4C | ENST00000482925.5 | n.2615C>G | non_coding_transcript_exon_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249422Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135444
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460838Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726726
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The c.2225C>G (p.S742C) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a C to G substitution at nucleotide position 2225, causing the serine (S) at amino acid position 742 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at L743 (P = 0.0439);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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