9-89363482-C-T

Position:

chr9-89363482-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001142287.2(SEMA4D):c.2138G>A(p.Arg713Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,984 control chromosomes in the GnomAD database, including 20,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1809 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18448 hom. )

Consequence

SEMA4D
NM_001142287.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.280

Variant links:

Genes affected

SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4D links:

SEMA4D (HGNC:):

SEMA4D links:

SECISBP2 (HGNC:30972): (SECIS binding protein 2) The protein encoded by this gene is one of the essential components of the machinery involved in co-translational insertion of selenocysteine (Sec) into selenoproteins. Sec is encoded by the UGA codon, which normally signals translation termination. The recoding of UGA as Sec codon requires a Sec insertion sequence (SECIS) element; present in the 3' untranslated regions of eukaryotic selenoprotein mRNAs. This protein specifically binds to the SECIS element, which is stimulated by a Sec-specific translation elongation factor. Mutations in this gene have been associated with reduction in enzymatic activity of type II iodothyronine deiodinase (a selenoprotein) and abnormal thyroid hormone metabolism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]

SECISBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.0554357E-4).

BP6

Variant 9-89363482-C-T is Benign according to our data. Variant chr9-89363482-C-T is described in ClinVar as [Benign]. Clinvar id is 3060820.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
SEMA4D	NM_001142287.2 linkuse as main transcript	c.2138G>A	p.Arg713Lys	missense_variant	20/21	NP_001135759.1	Q92854-2
SEMA4D	NM_001371198.1 linkuse as main transcript	c.2138G>A	p.Arg713Lys	missense_variant	18/19	NP_001358127.1
SEMA4D	NM_001371199.1 linkuse as main transcript	c.2138G>A	p.Arg713Lys	missense_variant	19/20	NP_001358128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
SEMA4D	ENST00000420101.6 linkuse as main transcript	c.293G>A	p.Arg98Lys	missense_variant	2/3	1	ENSP00000399948.2	A0A0C4DG45
SEMA4D	ENST00000475255.5 linkuse as main transcript	n.2173G>A		non_coding_transcript_exon_variant	1/2	1
SEMA4D	ENST00000339861.8 linkuse as main transcript	c.2138G>A	p.Arg713Lys	missense_variant	18/19	5	ENSP00000344923.4	Q92854-2

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19385

AN:

152144

Hom.:

1801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.178

AC:

44590

AN:

251200

Hom.:

6020

AF XY:

0.167

AC XY:

22654

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.0820

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.145

AC:

212484

AN:

1461722

Hom.:

18448

Cov.:

AF XY:

0.143

AC XY:

104305

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0364

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.0832

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.127

AC:

19410

AN:

152262

Hom.:

1809

Cov.:

AF XY:

0.131

AC XY:

9771

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0433

Gnomad4 AMR

AF:

0.295

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.125

Hom.:

1384

Bravo

AF:

0.136

TwinsUK

AF:

0.130

AC:

482

ALSPAC

AF:

0.141

AC:

544

ESP6500AA

AF:

0.0418

AC:

184

ESP6500EA

AF:

0.133

AC:

1147

ExAC

AF:

0.163

AC:

19730

Asia WGS

AF:

0.193

AC:

670

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA4D-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.38

.;T;T;.

MetaRNN

Benign

0.00091

T;T;T;T

MetaSVM

Benign

-0.91

PROVEAN

Benign

-0.090

N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.47

T;T;T;T

Sift4G

Benign

0.42

T;T;D;T

Polyphen

0.0040

B;B;.;B

Vest4

0.10

ClinPred

0.0021

GERP RS

0.79

Splicing

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