Variant 3-50270214-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001290060.2(SEMA3B):c.197G>A(p.Arg66His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000857 in 1,610,278 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

SEMA3B
NM_001290060.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.87

Variant links:

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SEMA3B	NM_001290060.2 linkuse as main transcript	c.197G>A	p.Arg66His	missense_variant	2/17	ENST00000616701.5	NP_001276989.1
SEMA3B	NM_001290061.1 linkuse as main transcript	c.197G>A	p.Arg66His	missense_variant	2/17		NP_001276990.1
SEMA3B	NM_004636.4 linkuse as main transcript	c.197G>A	p.Arg66His	missense_variant	3/18		NP_004627.1
SEMA3B	NM_001005914.3 linkuse as main transcript	c.197G>A	p.Arg66His	missense_variant	3/18		NP_001005914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3B	ENST00000616701.5 linkuse as main transcript	c.197G>A	p.Arg66His	missense_variant	2/17	1	NM_001290060.2	ENSP00000484146	P5	Q13214-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

242968

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

132114

show subpopulations

Gnomad AFR exome

AF:

0.0000684

Gnomad AMR exome

AF:

0.000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000908

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.0000850

AC:

124

AN:

1458146

Hom.:

Cov.:

AF XY:

0.0000869

AC XY:

AN XY:

725056

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000384

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000500

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000743

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3B-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 27, 2024

The SEMA3B c.197G>A variant is predicted to result in the amino acid substitution p.Arg66His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.0085

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.14

.;T;T;.;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;.;D;D

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Uncertain

-0.010

PrimateAI

Uncertain

0.68

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

1.0

.;D;D;.;.

Vest4

0.80, 0.80, 0.80, 0.78

MVP

0.30

ClinPred

0.93

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.83

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