Variant 5-9044535-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003966.3(SEMA5A):c.2943C>T(p.Leu981=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,750 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 32)

Exomes 𝑓: 0.019 ( 373 hom. )

Consequence

SEMA5A
NM_003966.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.372

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:

(HGNC:):

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 (BayesDel_noAF=-0.69).

BP6

Variant 5-9044535-G-A is Benign according to our data. Variant chr5-9044535-G-A is described in ClinVar as [Benign]. Clinvar id is 3059430.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.372 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2183/152216) while in subpopulation NFE AF= 0.0207 (1405/68012). AF 95% confidence interval is 0.0198. There are 25 homozygotes in gnomad4. There are 977 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3 linkuse as main transcript	c.2943C>T	p.Leu981=	synonymous_variant	22/23	ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SEMA5A	ENST00000382496.10 linkuse as main transcript	c.2943C>T	p.Leu981=	synonymous_variant	22/23	1	NM_003966.3	P1
	ENST00000506519.1 linkuse as main transcript	n.669+1258G>A		intron_variant, non_coding_transcript_variant		3
SEMA5A	ENST00000652226.1 linkuse as main transcript	c.2943C>T	p.Leu981=	synonymous_variant	24/25			P1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2186

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00910

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00604

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0117

AC:

2929

AN:

251350

Hom.:

AF XY:

0.0117

AC XY:

1596

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.00679

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0192

AC:

28115

AN:

1461534

Hom.:

373

Cov.:

AF XY:

0.0187

AC XY:

13564

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.00601

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00292

Gnomad4 FIN exome

AF:

0.00728

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0143

AC:

2183

AN:

152216

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

977

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00905

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00604

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0193

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA5A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 09, 2019

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.5

DANN

Benign

0.88

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