Variant 2-74657599-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004263.5(SEMA4F):c.332A>G(p.Asn111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEMA4F
NM_004263.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.234

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102556676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4F	NM_004263.5 linkuse as main transcript	c.332A>G	p.Asn111Ser	missense_variant	3/14	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.332A>G	p.Asn111Ser	missense_variant	3/14	1	NM_004263.5	ENSP00000350547.2		O95754-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251492

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 08, 2023

The c.332A>G (p.N111S) alteration is located in exon 3 (coding exon 3) of the SEMA4F gene. This alteration results from a A to G substitution at nucleotide position 332, causing the asparagine (N) at amino acid position 111 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.029

T;.;.;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.78

T;T;T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.84

N;.;N;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.10

N;.;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.28

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.012

B;.;B;B;.

Vest4

0.10

MutPred

0.35

Gain of phosphorylation at N111 (P = 0.0185);Gain of phosphorylation at N111 (P = 0.0185);Gain of phosphorylation at N111 (P = 0.0185);Gain of phosphorylation at N111 (P = 0.0185);Gain of phosphorylation at N111 (P = 0.0185);

MVP

0.085

MPC

0.18

ClinPred

0.14

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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