3-50159659-C-T

Position:

• chr3-50159659-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004186.5(SEMA3F):​c.37C>T​(p.Leu13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,612,908 control chromosomes in the GnomAD database, including 11,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (1579 hom., cov: 33)
  • Exomes 𝑓: 0.032 (10228 hom.)
• Consequence: SEMA3F NM_004186.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.92

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-50159659-C-T is Benign according to our data. Variant chr3-50159659-C-T is described in ClinVar as [Benign]. Clinvar id is 3060222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3F	NM_004186.5	c.37C>T	p.Leu13=	synonymous_variant	2/19	ENST00000002829.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3F	ENST00000002829.8	c.37C>T	p.Leu13=	synonymous_variant	2/19	1	NM_004186.5

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8205 AN: 152234 Hom.: 1578 Cov.: 33

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.0597

GnomAD3 exomes AF: 0.110 AC: 27343 AN: 249582 Hom.: 6732 AF XY: 0.0906 AC XY: 12252 AN XY: 135220

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.00707

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.0108

Gnomad FIN exome AF: 0.0472

Gnomad NFE exome AF: 0.00393

Gnomad OTH exome AF: 0.0627

GnomAD4 exome AF: 0.0325 AC: 47463 AN: 1460556 Hom.: 10228 Cov.: 29 AF XY: 0.0300 AC XY: 21767 AN XY: 726624

Gnomad4 AFR exome AF: 0.00475

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.00777

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0474

Gnomad4 NFE exome AF: 0.00188

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0539 AC: 8212 AN: 152352 Hom.: 1579 Cov.: 33 AF XY: 0.0623 AC XY: 4645 AN XY: 74502

Gnomad4 AFR AF: 0.00779

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.00332

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0119 Hom.: 98

Bravo AF: 0.0723

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SEMA3F-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2072053; hg19: chr3-50197092;