2-96860716-G-C

Variant names:

• chr2-96860716-G-C
• rs772927998
• NM_017789.5:c.2412C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017789.5(SEMA4C):​c.2412C>G​(p.His804Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA4C NM_017789.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05198592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4C	NM_017789.5	c.2412C>G	p.His804Gln	missense_variant	Exon 15 of 15	ENST00000305476.10	NP_060259.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4C	ENST00000305476.10	c.2412C>G	p.His804Gln	missense_variant	Exon 15 of 15	1	NM_017789.5	ENSP00000306844.5
SEMA4C	ENST00000467747.1	n.2403C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
SEMA4C	ENST00000474420.1	n.1645C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
SEMA4C	ENST00000482925.5	n.2802C>G		non_coding_transcript_exon_variant	Exon 13 of 13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.63
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.026
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.024	B
Vest4		0.14
MutPred		0.11		Loss of methylation at R799 (P = 0.0794);
MVP		0.13
MPC		0.29
ClinPred		0.071	T
GERP RS		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.060
gMVP		0.16
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs772927998; hg19: chr2-97526453;