Variant 7-84999836-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001384900.1(SEMA3D):c.1938G>A(p.Thr646=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,613,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

SEMA3D
NM_001384900.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.90

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-84999836-C-T is Benign according to our data. Variant chr7-84999836-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 742221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.9 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3D	NM_001384900.1 linkuse as main transcript	c.1938G>A	p.Thr646=	synonymous_variant	19/19	ENST00000284136.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3D	ENST00000284136.11 linkuse as main transcript	c.1938G>A	p.Thr646=	synonymous_variant	19/19	5	NM_001384900.1	P1
SEMA3D	ENST00000484038.1 linkuse as main transcript	n.1064G>A		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000180

AC:

AN:

250450

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000671

AC:

AN:

1461110

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.000170

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SEMA3D-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 26, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

Cadd

Benign

7.3

Dann

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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