7-80745001-G-C

Variant summary

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

The NM_006379.5(SEMA3C):​c.2149C>G​(p.Gln717Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SEMA3C
NM_006379.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62
Variant links:
Genes affected
SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

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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=0.10473889).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA3CNM_006379.5 linkc.2149C>G p.Gln717Glu missense_variant Exon 18 of 18 ENST00000265361.8 NP_006370.1 Q99985-1
SEMA3CNM_001350120.2 linkc.2203C>G p.Gln735Glu missense_variant Exon 18 of 18 NP_001337049.1
SEMA3CNM_001350121.2 linkc.1975C>G p.Gln659Glu missense_variant Exon 19 of 19 NP_001337050.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA3CENST00000265361.8 linkc.2149C>G p.Gln717Glu missense_variant Exon 18 of 18 1 NM_006379.5 ENSP00000265361.3 Q99985-1
SEMA3CENST00000419255.6 linkc.2149C>G p.Gln717Glu missense_variant Exon 18 of 18 2 ENSP00000411193.2 Q99985-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461792
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Benign
0.48
DEOGEN2
Benign
0.079
T;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.36
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.73
.;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.54
N;N
REVEL
Benign
0.045
Sift
Benign
0.28
T;T
Sift4G
Benign
0.65
T;T
Polyphen
0.0
B;B
Vest4
0.23
MVP
0.30
MPC
0.16
ClinPred
0.57
D
GERP RS
4.5
Varity_R
0.13
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-80374317; API