Variant chr7-84999673-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001384900.1(SEMA3D):c.2101A>C(p.Lys701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,526 control chromosomes in the GnomAD database, including 81,188 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 7942 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73246 hom. )

Consequence

SEMA3D
NM_001384900.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

SEMA3D 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=0.003791988).

BP6

Variant 7-84999673-T-G is Benign according to our data. Variant chr7-84999673-T-G is described in ClinVar as [Benign]. Clinvar id is 3060976.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3D	NM_001384900.1 linkuse as main transcript	c.2101A>C	p.Lys701Gln	missense_variant	19/19	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11 linkuse as main transcript	c.2101A>C	p.Lys701Gln	missense_variant	19/19	5	NM_001384900.1	ENSP00000284136	P1
SEMA3D	ENST00000484038.1 linkuse as main transcript	n.1227A>C		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48715

AN:

151768

Hom.:

7934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.281

AC:

70729

AN:

251380

Hom.:

10654

AF XY:

0.283

AC XY:

38415

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.313

AC:

457173

AN:

1461642

Hom.:

73246

Cov.:

AF XY:

0.310

AC XY:

225403

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.321

AC:

48743

AN:

151884

Hom.:

7942

Cov.:

AF XY:

0.315

AC XY:

23356

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.283

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.323

Hom.:

17254

Bravo

AF:

0.324

TwinsUK

AF:

0.315

AC:

1169

ALSPAC

AF:

0.329

AC:

1268

ESP6500AA

AF:

0.373

AC:

1642

ESP6500EA

AF:

0.327

AC:

2814

ExAC

AF:

0.287

AC:

34869

Asia WGS

AF:

0.223

AC:

776

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.325

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3D-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

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

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.24

REVEL

Benign

0.10

Sift

Benign

0.66

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.015

MPC

0.16

ClinPred

0.0016

GERP RS

3.8

Varity_R

0.092

gMVP

0.22

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