12-71139801-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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 GnomAd at 8 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152168 Hom.: 8 Cov.: 33

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.: 22 AF XY: 0.00486 AC XY: 659 AN XY: 135606

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.: 84 Cov.: 32 AF XY: 0.00249 AC XY: 1807 AN XY: 727152

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.: 8 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74468

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.: 0

Bravo AF: 0.00232

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.000328

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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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

Other links and lift over

dbSNP: rs118147203; hg19: chr12-71533581; COSMIC: COSV56080141; COSMIC: COSV56080141;