Variant 2-74656681-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004263.5(SEMA4F):c.293G>A(p.Arg98His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

SEMA4F
NM_004263.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

SEMA4F (HGNC:10734): (ssemaphorin 4F) This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SEMA4F links:

SEMA4F (HGNC:):

SEMA4F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0245848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4F	NM_004263.5 linkuse as main transcript	c.293G>A	p.Arg98His	missense_variant	2/14	ENST00000357877.7	NP_004254.2	O95754-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4F	ENST00000357877.7 linkuse as main transcript	c.293G>A	p.Arg98His	missense_variant	2/14	1	NM_004263.5	ENSP00000350547.2		O95754-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251336

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000740

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.293G>A (p.R98H) alteration is located in exon 2 (coding exon 2) of the SEMA4F gene. This alteration results from a G to A substitution at nucleotide position 293, causing the arginine (R) at amino acid position 98 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;.;.;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.054

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.0052

MetaRNN

Benign

0.025

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.80

N;.;N;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.48

N;.;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.56

T;.;T;T;T

Sift4G

Uncertain

0.058

T;T;D;T;D

Polyphen

0.020

B;.;B;D;.

Vest4

0.31

MutPred

0.50

Loss of catalytic residue at R98 (P = 0.011);Loss of catalytic residue at R98 (P = 0.011);Loss of catalytic residue at R98 (P = 0.011);Loss of catalytic residue at R98 (P = 0.011);Loss of catalytic residue at R98 (P = 0.011);

MVP

0.13

MPC

0.28

ClinPred

0.11

GERP RS

1.9

Varity_R

0.052

gMVP

0.40

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