chr3-50159717-T-A

Variant names:

• chr3-50159717-T-A
• NM_004186.5:c.95T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004186.5(SEMA3F):​c.95T>A​(p.Val32Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA3F NM_004186.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.48

Genes affected

SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.95T>A	p.Val32Asp	missense_variant	Exon 2 of 19	ENST00000002829.8	NP_004177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3F	ENST00000002829.8	c.95T>A	p.Val32Asp	missense_variant	Exon 2 of 19	1	NM_004186.5	ENSP00000002829.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SEMA3F-related disorder Uncertain:1

Aug 21, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The SEMA3F c.95T>A variant is predicted to result in the amino acid substitution p.Val32Asp. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T;T;T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	.;.;M;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		0.87	.;.;P;.;.
Vest4		0.74, 0.78
MutPred		0.71		Gain of disorder (P = 0.0033);Gain of disorder (P = 0.0033);Gain of disorder (P = 0.0033);Gain of disorder (P = 0.0033);Gain of disorder (P = 0.0033);
MVP		0.57
MPC		0.72
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.84
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr3-50197150;