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GeneBe

1-151133151-A-G

Variant summary

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

The NM_030913.6(SEMA6C):c.2126T>C(p.Val709Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,552,398 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
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=0.026262581).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6CNM_030913.6 linkuse as main transcriptc.2126T>C p.Val709Ala missense_variant 19/19 ENST00000368914.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6CENST00000368914.8 linkuse as main transcriptc.2126T>C p.Val709Ala missense_variant 19/191 NM_030913.6 P4Q9H3T2-1
SEMA6CENST00000368913.7 linkuse as main transcriptc.2222T>C p.Val741Ala missense_variant 20/201 A1Q9H3T2-3
SEMA6CENST00000341697.7 linkuse as main transcriptc.2126T>C p.Val709Ala missense_variant 19/191 P4Q9H3T2-1
SEMA6CENST00000368912.7 linkuse as main transcriptc.2102T>C p.Val701Ala missense_variant 19/191 Q9H3T2-2

Frequencies

GnomAD3 genomes
AF:
0.0000199
AC:
3
AN:
150528
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000198
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000577
AC:
10
AN:
173352
Hom.:
0
AF XY:
0.0000307
AC XY:
3
AN XY:
97704
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000397
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000785
AC:
11
AN:
1401870
Hom.:
0
Cov.:
33
AF XY:
0.00000574
AC XY:
4
AN XY:
696434
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000305
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000199
AC:
3
AN:
150528
Hom.:
0
Cov.:
32
AF XY:
0.0000272
AC XY:
2
AN XY:
73498
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000198
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000699
AC:
8

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 GeneticsAug 16, 2021The c.2222T>C (p.V741A) alteration is located in exon 20 (coding exon 18) of the SEMA6C gene. This alteration results from a T to C substitution at nucleotide position 2222, causing the valine (V) at amino acid position 741 to be replaced by an alanine (A). 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
0.081
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.75
Cadd
Benign
15
Dann
Benign
0.85
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.73
T;T;.;T
M_CAP
Benign
0.078
D
MetaRNN
Benign
0.026
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.81
N;N;N;N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.14
N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.21
T;T;T;T
Sift4G
Benign
0.70
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.039
MutPred
0.11
.;.;Loss of methylation at K710 (P = 0.0479);Loss of methylation at K710 (P = 0.0479);
MVP
0.29
MPC
0.73
ClinPred
0.043
T
GERP RS
1.4
Varity_R
0.033
gMVP
0.23

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: rs759281048; hg19: chr1-151105627; API