Genetic Variant SEMA3F:p.Thr14Thr (chr3-50159664-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_004186.5(SEMA3F):c.42C>T(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,610,692 control chromosomes in the GnomAD database, including 145,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 11829 hom., cov: 33)

Exomes 𝑓: 0.42 ( 133351 hom. )

Consequence

SEMA3F
NM_004186.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.943

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 3-50159664-C-T is Benign according to our data. Variant chr3-50159664-C-T is described in ClinVar as [Benign]. Clinvar id is 3060562.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.943 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3F	NM_004186.5 link	c.42C>T	p.Thr14Thr	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.42C>T	p.Thr14Thr	synonymous_variant	Exon 2 of 19	1	NM_004186.5	ENSP00000002829.3		Q13275-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58790

AN:

151982

Hom.:

11822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.378

GnomAD3 exomes

AF:

0.411

AC:

102445

AN:

249386

Hom.:

23157

AF XY:

0.430

AC XY:

58077

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.420

AC:

612973

AN:

1458590

Hom.:

133351

Cov.:

AF XY:

0.429

AC XY:

311006

AN XY:

725740

show subpopulations

Gnomad4 AFR exome

AF:

0.325

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.665

Gnomad4 FIN exome

AF:

0.448

Gnomad4 NFE exome

AF:

0.417

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.387

AC:

58820

AN:

152102

Hom.:

11829

Cov.:

AF XY:

0.391

AC XY:

29042

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.663

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.402

Hom.:

5376

Bravo

AF:

0.360

Asia WGS

AF:

0.461

AC:

1606

AN:

3478

EpiCase

AF:

0.426

EpiControl

AF:

0.419

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3F-related disorder

Benign:1

Apr 11, 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

-0.46

CADD

Benign

8.3

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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