3-50159665-G-C

Position:

• chr3-50159665-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000002829.8(SEMA3F):​c.43G>C​(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,612,550 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.039 (375 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (356 hom.)
• Consequence: SEMA3F ENST00000002829.8 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.67

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017032325).
• BP6: Variant 3-50159665-G-C is Benign according to our data. Variant chr3-50159665-G-C is described in ClinVar as [Benign]. Clinvar id is 3057219.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.43G>C	p.Gly15Arg	missense_variant	2/19	ENST00000002829.8	NP_004177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3F	ENST00000002829.8	c.43G>C	p.Gly15Arg	missense_variant	2/19	1	NM_004186.5	ENSP00000002829

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5872 AN: 152184 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0104 AC: 2589 AN: 249682 Hom.: 165 AF XY: 0.00763 AC XY: 1032 AN XY: 135236

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.00662

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000619

Gnomad OTH exome AF: 0.00559

GnomAD4 exome AF: 0.00413 AC: 6037 AN: 1460248 Hom.: 356 Cov.: 31 AF XY: 0.00359 AC XY: 2605 AN XY: 726476

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.00752

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000333

Gnomad4 OTH exome AF: 0.00905

GnomAD4 genome AF: 0.0387 AC: 5887 AN: 152302 Hom.: 375 Cov.: 33 AF XY: 0.0369 AC XY: 2749 AN XY: 74486

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00432 Hom.: 7

Bravo AF: 0.0451

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.141 AC: 620

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0126 AC: 1525

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000437

EpiControl AF: 0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SEMA3F-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 22, 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
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
MetaRNN	Benign	0.0017	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;.;L;.;L
MutationTaster	Benign	0.80	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.14	T;T;T;T;T
Sift4G	Benign	0.57	T;T;T;T;T
Polyphen		0.98	.;.;D;.;.
Vest4		0.54, 0.26
MutPred		0.47		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MPC		0.27
ClinPred		0.019	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.44

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

Other links and lift over

dbSNP: rs61751940; hg19: chr3-50197098;