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GeneBe

1-151132845-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030913.6(SEMA6C):c.2432C>T(p.Pro811Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,283,022 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 (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101
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 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=0.08074176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6CNM_030913.6 linkuse as main transcriptc.2432C>T p.Pro811Leu missense_variant 19/19 ENST00000368914.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6CENST00000368914.8 linkuse as main transcriptc.2432C>T p.Pro811Leu missense_variant 19/191 NM_030913.6 P4Q9H3T2-1

Frequencies

GnomAD3 genomes
AF:
0.0000465
AC:
7
AN:
150580
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00174
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000371
AC:
42
AN:
1132442
Hom.:
0
Cov.:
29
AF XY:
0.0000475
AC XY:
26
AN XY:
547202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.00249
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000422
Gnomad4 OTH exome
AF:
0.0000671
GnomAD4 genome
AF:
0.0000465
AC:
7
AN:
150580
Hom.:
0
Cov.:
32
AF XY:
0.0000408
AC XY:
3
AN XY:
73522
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00174
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000356
Hom.:
0
Bravo
AF:
0.0000567

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 GeneticsOct 18, 2021The c.2528C>T (p.P843L) 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 2528, causing the proline (P) at amino acid position 843 to be replaced by a leucine (L). 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
0.079
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
Cadd
Benign
16
Dann
Uncertain
0.98
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.81
T;T;.;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.081
T;T;T;T
MetaSVM
Benign
-0.89
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Benign
0.17
T;T;T;T
Polyphen
0.18
B;D;B;B
Vest4
0.11
MutPred
0.22
.;.;Loss of glycosylation at P811 (P = 0.0664);Loss of glycosylation at P811 (P = 0.0664);
MVP
0.65
MPC
0.43
ClinPred
0.45
T
GERP RS
3.3
Varity_R
0.070
gMVP
0.55

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: rs1013641087; hg19: chr1-151105321; API