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GeneBe

2-96860840-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_017789.5(SEMA4C):c.2288C>T(p.Pro763Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,184 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 (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SEMA4C
NM_017789.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
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 Benign. Variant got -7 ACMG points.

PP2
Missense variant where missense usually causes diseases, SEMA4C
BP4
Computational evidence support a benign effect (MetaRNN=0.05662638).
BS2
High AC in GnomAd at 25 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA4CNM_017789.5 linkuse as main transcriptc.2288C>T p.Pro763Leu missense_variant 15/15 ENST00000305476.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA4CENST00000305476.10 linkuse as main transcriptc.2288C>T p.Pro763Leu missense_variant 15/151 NM_017789.5 P1
SEMA4CENST00000467747.1 linkuse as main transcriptn.2279C>T non_coding_transcript_exon_variant 3/32
SEMA4CENST00000474420.1 linkuse as main transcriptn.1521C>T non_coding_transcript_exon_variant 2/22
SEMA4CENST00000482925.5 linkuse as main transcriptn.2678C>T non_coding_transcript_exon_variant 13/132

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000603
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000400
AC:
10
AN:
249980
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135582
show subpopulations
Gnomad AFR exome
AF:
0.000625
Gnomad AMR exome
AF:
0.00
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:
0.0000151
AC:
22
AN:
1460956
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
726800
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.000603
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

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 30, 2023The c.2288C>T (p.P763L) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a C to T substitution at nucleotide position 2288, causing the proline (P) at amino acid position 763 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
0.10
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.28
Cadd
Benign
23
Dann
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.097
D
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.17
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.011
D
Polyphen
0.058
B
Vest4
0.26
MVP
0.21
MPC
0.30
ClinPred
0.069
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.26

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: rs149552418; hg19: chr2-97526577; API