Variant X-38675779-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004615.4(TSPAN7):c.516C>A(p.Pro172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000649 in 1,209,123 control chromosomes in the GnomAD database, including 3 homozygotes. There are 256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 17 hem., cov: 23)

Exomes 𝑓: 0.00066 ( 3 hom. 239 hem. )

Consequence

TSPAN7
NM_004615.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

TSPAN7 (HGNC:11854): (tetraspanin 7) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. This gene is associated with X-linked cognitive disability and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. [provided by RefSeq, Jul 2008]

TSPAN7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant X-38675779-C-A is Benign according to our data. Variant chrX-38675779-C-A is described in ClinVar as [Benign]. Clinvar id is 731385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN7	NM_004615.4 linkuse as main transcript	c.516C>A	p.Pro172=	synonymous_variant	5/8	ENST00000378482.7	NP_004606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN7	ENST00000378482.7 linkuse as main transcript	c.516C>A	p.Pro172=	synonymous_variant	5/8	1	NM_004615.4	ENSP00000367743	P1

Frequencies

GnomAD3 genomes

AF:

0.000576

AC:

AN:

111156

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

33344

show subpopulations

Gnomad AFR

AF:

0.0000655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00130

AC:

238

AN:

182961

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

67563

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.0000731

Gnomad ASJ exome

AF:

0.0268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000306

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.000657

AC:

721

AN:

1097967

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

239

AN XY:

363387

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.0265

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.000576

AC:

AN:

111156

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

33344

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.000578

EpiCase

AF:

0.000164

EpiControl

AF:

0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 14, 2019

- -

TSPAN7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 30, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.30

DANN

Benign

0.55

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