NM_004616.3:c.258G>A

Variant names:

• chr12-71139714-C-T
• rs117090819
• NM_004616.3:c.258G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004616.3(TSPAN8):​c.258G>A​(p.Leu86Leu) 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 1,613,310 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.132
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-71139714-C-T is Benign according to our data. Variant chr12-71139714-C-T is described in ClinVar as Benign. ClinVar VariationId is 779950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.132 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00263 (400/152268) while in subpopulation EAS AF = 0.0494 (255/5158). AF 95% confidence interval is 0.0445. There are 8 homozygotes in GnomAd4. There are 216 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.258G>A	p.Leu86Leu	synonymous	Exon 4 of 9	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.258G>A	p.Leu86Leu	synonymous	Exon 3 of 8	NP_001356689.1	P19075

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.258G>A	p.Leu86Leu	synonymous	Exon 4 of 9	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.258G>A	p.Leu86Leu	synonymous	Exon 7 of 12	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.258G>A	p.Leu86Leu	synonymous	Exon 3 of 8	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152150 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.000338

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: 0.00430

GnomAD2 exomes AF: 0.00478 AC: 1196 AN: 250336 AF XY: 0.00487

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00550

Gnomad EAS exome AF: 0.0414

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00227 AC: 3310 AN: 1461042 Hom.: 84 Cov.: 30 AF XY: 0.00249 AC XY: 1807 AN XY: 726836

African (AFR) AF: 0.000269 AC: 9 AN: 33464

American (AMR) AF: 0.000851 AC: 38 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00652 AC: 170 AN: 26056

East Asian (EAS) AF: 0.0495 AC: 1965 AN: 39690

South Asian (SAS) AF: 0.00902 AC: 777 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5748

European-Non Finnish (NFE) AF: 0.0000819 AC: 91 AN: 1111516

Other (OTH) AF: 0.00424 AC: 256 AN: 60358

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152268 Hom.: 8 Cov.: 33 AF XY: 0.00290 AC XY: 216 AN XY: 74458

African (AFR) AF: 0.000337 AC: 14 AN: 41570

American (AMR) AF: 0.00157 AC: 24 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.0494 AC: 255 AN: 5158

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68016

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.000726 Hom.: 1

Bravo AF: 0.00232

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.000328

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs117090819; hg19: chr12-71533494; COSMIC: COSV56078238; COSMIC: COSV56078238;