1-151133140-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030913.6(SEMA6C):c.2137C>T(p.Arg713Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,560,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00059 ( 1 hom. )
Consequence
SEMA6C
NM_030913.6 missense
NM_030913.6 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 3.19
Genes affected
SEMA6C (HGNC:10740): (semaphorin 6C) This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09115487).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6C | NM_030913.6 | c.2137C>T | p.Arg713Cys | missense_variant | 19/19 | ENST00000368914.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6C | ENST00000368914.8 | c.2137C>T | p.Arg713Cys | missense_variant | 19/19 | 1 | NM_030913.6 | P4 | |
SEMA6C | ENST00000368913.7 | c.2233C>T | p.Arg745Cys | missense_variant | 20/20 | 1 | A1 | ||
SEMA6C | ENST00000341697.7 | c.2137C>T | p.Arg713Cys | missense_variant | 19/19 | 1 | P4 | ||
SEMA6C | ENST00000368912.7 | c.2113C>T | p.Arg705Cys | missense_variant | 19/19 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000435 AC: 66AN: 151744Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000440 AC: 80AN: 181810Hom.: 0 AF XY: 0.000430 AC XY: 44AN XY: 102420
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GnomAD4 exome AF: 0.000587 AC: 826AN: 1408168Hom.: 1 Cov.: 33 AF XY: 0.000539 AC XY: 377AN XY: 699968
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GnomAD4 genome ? AF: 0.000435 AC: 66AN: 151856Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 34AN XY: 74254
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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 | Aug 10, 2021 | The c.2233C>T (p.R745C) alteration is located in exon 20 (coding exon 18) of the SEMA6C gene. This alteration results from a C to T substitution at nucleotide position 2233, causing the arginine (R) at amino acid position 745 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at