Variant 5-9050431-C-T 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_003966.3(SEMA5A):c.2872G>A(p.Val958Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,612,558 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 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

SEMA5A
NM_003966.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

SEMA5A 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=0.02491638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3 linkuse as main transcript	c.2872G>A	p.Val958Ile	missense_variant	21/23	ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5A	ENST00000382496.10 linkuse as main transcript	c.2872G>A	p.Val958Ile	missense_variant	21/23	1	NM_003966.3	P1
SEMA5A	ENST00000652226.1 linkuse as main transcript	c.2872G>A	p.Val958Ile	missense_variant	23/25			P1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000288

AC:

AN:

250128

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000352

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000485

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000301

AC:

440

AN:

1460398

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

726406

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000210

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000720

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000832

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

Nov 17, 2022

The c.2872G>A (p.V958I) alteration is located in exon 21 (coding exon 19) of the SEMA5A gene. This alteration results from a G to A substitution at nucleotide position 2872, causing the valine (V) at amino acid position 958 to be replaced by an isoleucine (I). 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

0.064

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.059

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.63

M_CAP

Benign

0.0042

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

MutationTaster

Benign

0.99

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.13

REVEL

Benign

0.018

Sift

Benign

0.71

Sift4G

Benign

0.98

Polyphen

0.0

Vest4

0.24

MVP

0.34

MPC

0.27

ClinPred

0.016

GERP RS

3.1

Varity_R

0.025

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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