Variant 3-122911499-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001031702.4(SEMA5B):c.3083A>G(p.Asp1028Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,607,440 control chromosomes in the GnomAD database, including 505,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.71 ( 40100 hom., cov: 33)

Exomes 𝑓: 0.79 ( 465492 hom. )

Consequence

SEMA5B
NM_001031702.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SEMA5B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4301991E-6).

BP6

Variant 3-122911499-T-C is Benign according to our data. Variant chr3-122911499-T-C is described in ClinVar as [Benign]. Clinvar id is 1230603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5B	NM_001031702.4 link	c.3083A>G	p.Asp1028Gly	missense_variant	21/23	ENST00000357599.8	NP_001026872.2	Q9P283-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5B	ENST00000357599.8 link	c.3083A>G	p.Asp1028Gly	missense_variant	21/23	1	NM_001031702.4	ENSP00000350215.3		Q9P283-1

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108438

AN:

151656

Hom.:

40087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.742

GnomAD3 exomes

AF:

0.709

AC:

169644

AN:

239390

Hom.:

63050

AF XY:

0.723

AC XY:

93153

AN XY:

128830

show subpopulations

Gnomad AFR exome

AF:

0.577

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.331

Gnomad SAS exome

AF:

0.731

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.792

AC:

1152565

AN:

1455666

Hom.:

465492

Cov.:

AF XY:

0.792

AC XY:

572558

AN XY:

723298

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.788

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.834

Gnomad4 OTH exome

AF:

0.767

GnomAD4 genome

AF:

0.715

AC:

108491

AN:

151774

Hom.:

40100

Cov.:

AF XY:

0.709

AC XY:

52531

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.585

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.776

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.733

Gnomad4 NFE

AF:

0.831

Gnomad4 OTH

AF:

0.743

Alfa

AF:

0.798

Hom.:

98012

Bravo

AF:

0.696

TwinsUK

AF:

0.834

AC:

3093

ALSPAC

AF:

0.835

AC:

3219

ESP6500AA

AF:

0.579

AC:

2552

ESP6500EA

AF:

0.832

AC:

7153

ExAC

AF:

0.713

AC:

85587

Asia WGS

AF:

0.588

AC:

2048

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.035

.;.;T;.;T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.068

T;T;T;T;.;T;T

MetaRNN

Benign

0.0000014

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N;.;N;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.31

.;N;.;.;N;.;N

REVEL

Benign

0.097

Sift

Benign

0.42

.;T;.;.;T;.;T

Sift4G

Benign

0.27

.;T;T;T;T;.;T

Polyphen

0.0

.;.;B;.;B;.;.

Vest4

0.071, 0.099, 0.12, 0.14

MPC

0.35

ClinPred

0.0011

GERP RS

3.2

Varity_R

0.056

gMVP

0.29

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