Variant 5-9050437-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003966.3(SEMA5A):c.2866A>G(p.Ser956Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,612,774 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 36 hom., cov: 33)

Exomes 𝑓: 0.016 ( 278 hom. )

Consequence

SEMA5A
NM_003966.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.42

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036143959).

BP6

Variant 5-9050437-T-C is Benign according to our data. Variant chr5-9050437-T-C is described in ClinVar as [Benign]. Clinvar id is 2655294.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2096/152338) while in subpopulation NFE AF= 0.0168 (1140/68028). AF 95% confidence interval is 0.0159. There are 36 homozygotes in gnomad4. There are 1109 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3 linkuse as main transcript	c.2866A>G	p.Ser956Gly	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.2866A>G	p.Ser956Gly	missense_variant	21/23	1	NM_003966.3	P1
SEMA5A	ENST00000652226.1 linkuse as main transcript	c.2866A>G	p.Ser956Gly	missense_variant	23/25			P1

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2096

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0140

AC:

3501

AN:

250124

Hom.:

AF XY:

0.0141

AC XY:

1903

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.00259

Gnomad AMR exome

AF:

0.00412

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.0508

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0156

AC:

22773

AN:

1460436

Hom.:

278

Cov.:

AF XY:

0.0150

AC XY:

10923

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.00422

Gnomad4 ASJ exome

AF:

0.0191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000991

Gnomad4 FIN exome

AF:

0.0502

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0138

AC:

2096

AN:

152338

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1109

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.00986

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0170

AC:

146

ExAC

AF:

0.0136

AC:

1654

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SEMA5A: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.076

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

REVEL

Benign

0.058

Sift

Benign

0.075

Sift4G

Benign

0.088

Polyphen

0.0010

Vest4

0.19

MPC

0.45

ClinPred

0.010

GERP RS

3.7

Varity_R

0.19

gMVP

0.54

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