2-74662749-G-C

Position:

• chr2-74662749-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004263.5(SEMA4F):​c.474G>C​(p.Gln158His) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA4F NM_004263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

Genes affected

SEMA4F (HGNC:10734): (ssemaphorin 4F) This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SEMA4F (HGNC:):

ACMG classification

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=0.1428532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4F	NM_004263.5	c.474G>C	p.Gln158His	missense_variant	5/14	ENST00000357877.7	NP_004254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4F	ENST00000357877.7	c.474G>C	p.Gln158His	missense_variant	5/14	1	NM_004263.5	ENSP00000350547.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.474G>C (p.Q158H) alteration is located in exon 5 (coding exon 5) of the SEMA4F gene. This alteration results from a G to C substitution at nucleotide position 474, causing the glutamine (Q) at amino acid position 158 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.13	N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.60	N;.;N
REVEL	Benign	0.033
Sift	Benign	0.11	T;.;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.31
MutPred		0.40		Gain of catalytic residue at R156 (P = 0.0971);.;.;
MVP		0.29
MPC		0.21
ClinPred		0.29	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.50

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: chr2-74889876;