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GeneBe

1-151136113-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030913.6(SEMA6C):c.1157G>A(p.Arg386Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.648
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04551503).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6CNM_030913.6 linkuse as main transcriptc.1157G>A p.Arg386Gln missense_variant 13/19 ENST00000368914.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6CENST00000368914.8 linkuse as main transcriptc.1157G>A p.Arg386Gln missense_variant 13/191 NM_030913.6 P4Q9H3T2-1
SEMA6CENST00000368913.7 linkuse as main transcriptc.1157G>A p.Arg386Gln missense_variant 13/201 A1Q9H3T2-3
SEMA6CENST00000341697.7 linkuse as main transcriptc.1157G>A p.Arg386Gln missense_variant 13/191 P4Q9H3T2-1
SEMA6CENST00000368912.7 linkuse as main transcriptc.1037G>A p.Arg346Gln missense_variant 12/191 Q9H3T2-2

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
151986
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000143
AC:
36
AN:
251414
Hom.:
0
AF XY:
0.000140
AC XY:
19
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000255
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000125
AC:
183
AN:
1461848
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
88
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000152
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000921
AC:
14
AN:
151986
Hom.:
0
Cov.:
31
AF XY:
0.0000808
AC XY:
6
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000160
Hom.:
0
Bravo
AF:
0.000121
ExAC
AF:
0.000157
AC:
19
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

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 submitterclinical testingAmbry GeneticsJul 14, 2021The c.1157G>A (p.R386Q) alteration is located in exon 13 (coding exon 11) of the SEMA6C gene. This alteration results from a G to A substitution at nucleotide position 1157, causing the arginine (R) at amino acid position 386 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.76
Cadd
Benign
21
Dann
Uncertain
0.99
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.83
T;T;.;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.046
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.68
N;.;N;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.020
N;N;N;N
REVEL
Benign
0.060
Sift
Benign
0.39
T;T;T;T
Sift4G
Benign
0.16
T;T;T;T
Polyphen
0.029
B;B;B;B
Vest4
0.29
MVP
0.31
MPC
0.81
ClinPred
0.087
T
GERP RS
3.5
Varity_R
0.051
gMVP
0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781152823; hg19: chr1-151108589; API