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GeneBe

2-96861030-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_017789.5(SEMA4C):c.2098G>A(p.Ala700Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,652 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: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SEMA4C
NM_017789.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2
Missense variant where missense usually causes diseases, SEMA4C
BP4
Computational evidence support a benign effect (MetaRNN=0.05513248).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA4CNM_017789.5 linkuse as main transcriptc.2098G>A p.Ala700Thr missense_variant 15/15 ENST00000305476.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA4CENST00000305476.10 linkuse as main transcriptc.2098G>A p.Ala700Thr missense_variant 15/151 NM_017789.5 P1
SEMA4CENST00000467747.1 linkuse as main transcriptn.2089G>A non_coding_transcript_exon_variant 3/32
SEMA4CENST00000474420.1 linkuse as main transcriptn.1331G>A non_coding_transcript_exon_variant 2/22
SEMA4CENST00000482925.5 linkuse as main transcriptn.2488G>A non_coding_transcript_exon_variant 13/132

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249454
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135446
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460652
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726606
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000165
AC:
2

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 04, 2022The c.2098G>A (p.A700T) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a G to A substitution at nucleotide position 2098, causing the alanine (A) at amino acid position 700 to be replaced by a threonine (T). 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
-0.26
T
BayesDel_noAF
Benign
-0.43
Cadd
Benign
18
Dann
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.73
T
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.96
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.20
Sift
Benign
0.035
D
Sift4G
Benign
0.35
T
Polyphen
0.17
B
Vest4
0.062
MutPred
0.18
Gain of phosphorylation at A700 (P = 0.0131);
MVP
0.24
MPC
0.28
ClinPred
0.069
T
GERP RS
4.1
Varity_R
0.075
gMVP
0.40

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: rs759008962; hg19: chr2-97526767; API