Variant 12-71139801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004616.3(TSPAN8):c.171C>T(p.Asp57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,990 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 84 hom. )

Consequence

TSPAN8
NM_004616.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0100

Variant links:

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) 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 that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

TSPAN8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-71139801-G-A is Benign according to our data. Variant chr12-71139801-G-A is described in ClinVar as [Benign]. Clinvar id is 779951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00263 (400/152286) while in subpopulation EAS AF= 0.0494 (256/5180). AF 95% confidence interval is 0.0445. There are 8 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN8	NM_004616.3 linkuse as main transcript	c.171C>T	p.Asp57=	synonymous_variant	4/9	ENST00000247829.8
TSPAN8	NM_001369760.1 linkuse as main transcript	c.171C>T	p.Asp57=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TSPAN8	ENST00000247829.8 linkuse as main transcript	c.171C>T	p.Asp57=	synonymous_variant	4/9	1	NM_004616.3	P1
TSPAN8	ENST00000393330.6 linkuse as main transcript	c.171C>T	p.Asp57=	synonymous_variant	7/12	1		P1
TSPAN8	ENST00000546561.2 linkuse as main transcript	c.171C>T	p.Asp57=	synonymous_variant	3/8	1		P1
TSPAN8	ENST00000552786.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

398

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0493

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00477

AC:

1196

AN:

250960

Hom.:

AF XY:

0.00486

AC XY:

659

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00547

Gnomad EAS exome

AF:

0.0413

Gnomad SAS exome

AF:

0.00941

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00227

AC:

3311

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1807

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00651

Gnomad4 EAS exome

AF:

0.0495

Gnomad4 SAS exome

AF:

0.00901

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.00424

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152286

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0494

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.000756

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.000328

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.54

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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