2-96860789-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017789.5(SEMA4C):ā€‹c.2339G>Cā€‹(p.Gly780Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00018 ( 0 hom., cov: 33)
Exomes š‘“: 0.00013 ( 0 hom. )

Consequence

SEMA4C
NM_017789.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79
Variant links:
Genes affected
SEMA4C (HGNC:10731): (semaphorin 4C) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16919386).
BS2
High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEMA4CNM_017789.5 linkuse as main transcriptc.2339G>C p.Gly780Ala missense_variant 15/15 ENST00000305476.10 NP_060259.4 Q9C0C4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEMA4CENST00000305476.10 linkuse as main transcriptc.2339G>C p.Gly780Ala missense_variant 15/151 NM_017789.5 ENSP00000306844.5 Q9C0C4
SEMA4CENST00000467747.1 linkuse as main transcriptn.2330G>C non_coding_transcript_exon_variant 3/32
SEMA4CENST00000474420.1 linkuse as main transcriptn.1572G>C non_coding_transcript_exon_variant 2/22
SEMA4CENST00000482925.5 linkuse as main transcriptn.2729G>C non_coding_transcript_exon_variant 13/132

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000323
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000637
AC:
16
AN:
251012
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.000123
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000125
AC:
183
AN:
1461446
Hom.:
0
Cov.:
31
AF XY:
0.000127
AC XY:
92
AN XY:
727052
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000377
Gnomad4 NFE exome
AF:
0.000156
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000248
Hom.:
0
Bravo
AF:
0.000151
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 GeneticsMar 15, 2024The c.2339G>C (p.G780A) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a G to C substitution at nucleotide position 2339, causing the glycine (G) at amino acid position 780 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
0.089
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.082
T
Eigen
Benign
0.18
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.54
N
REVEL
Benign
0.11
Sift
Benign
0.10
T
Sift4G
Benign
0.25
T
Polyphen
1.0
D
Vest4
0.23
MVP
0.24
MPC
0.41
ClinPred
0.10
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.21

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

LitVar

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

Other links and lift over

dbSNP: rs768846129; hg19: chr2-97526526; API