Genetic Variant SEMA3F:p.Leu13Leu (chr3-50159659-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004186.5(SEMA3F):c.37C>T(p.Leu13Leu) 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 (no stars).

Frequency

Genomes: 𝑓 0.054 ( 1579 hom., cov: 33)

Exomes 𝑓: 0.032 ( 10228 hom. )

Consequence

SEMA3F
NM_004186.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.92

Variant links:

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]

SEMA3F links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
SEMA3F	NM_004186.5 link	c.37C>T	p.Leu13Leu	synonymous_variant	Exon 2 of 19	ENST00000002829.8	NP_004177.3	Q13275-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3F	ENST00000002829.8 link	c.37C>T	p.Leu13Leu	synonymous_variant	Exon 2 of 19	1	NM_004186.5	ENSP00000002829.3		Q13275-1

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8205

AN:

152234

Hom.:

1578

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0300

AC XY:

21767

AN XY:

726624

show subpopulations

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.:

AF XY:

0.0623

AC XY:

4645

AN XY:

74502

show subpopulations

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.:

Bravo

AF:

0.0723

Asia WGS

AF:

0.205

AC:

711

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3F-related disorder

Benign:1

Sep 24, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over