rs17849952

Variant names:

• chr12-71144171-C-T
• rs17849952
• NM_004616.3:c.103G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004616.3(TSPAN8):​c.103G>A​(p.Val35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,611,794 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (11 hom., cov: 32)
  • Exomes 𝑓: 0.012 (130 hom.)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.701
• Publications: 11 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008988857).
• BP6: Variant 12-71144171-C-T is Benign according to our data. Variant chr12-71144171-C-T is described in ClinVar as Benign. ClinVar VariationId is 710022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 11 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.103G>A	p.Val35Ile	missense	Exon 3 of 9	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.103G>A	p.Val35Ile	missense	Exon 2 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.103G>A	p.Val35Ile	missense	Exon 3 of 9	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.103G>A	p.Val35Ile	missense	Exon 6 of 12	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.103G>A	p.Val35Ile	missense	Exon 2 of 8	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes AF: 0.00971 AC: 1476 AN: 152032 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00944 AC: 2359 AN: 249804 AF XY: 0.00980

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00279

Gnomad ASJ exome AF: 0.00528

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.00854

GnomAD4 exome AF: 0.0121 AC: 17709 AN: 1459644 Hom.: 130 Cov.: 30 AF XY: 0.0120 AC XY: 8711 AN XY: 726158

African (AFR) AF: 0.00185 AC: 62 AN: 33436

American (AMR) AF: 0.00282 AC: 126 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00460 AC: 120 AN: 26082

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39630

South Asian (SAS) AF: 0.00618 AC: 532 AN: 86124

European-Finnish (FIN) AF: 0.0266 AC: 1398 AN: 52602

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5748

European-Non Finnish (NFE) AF: 0.0134 AC: 14862 AN: 1111052

Other (OTH) AF: 0.00982 AC: 592 AN: 60312

GnomAD4 genome AF: 0.00969 AC: 1475 AN: 152150 Hom.: 11 Cov.: 32 AF XY: 0.0102 AC XY: 758 AN XY: 74348

African (AFR) AF: 0.00214 AC: 89 AN: 41534

American (AMR) AF: 0.00236 AC: 36 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00685 AC: 33 AN: 4816

European-Finnish (FIN) AF: 0.0321 AC: 339 AN: 10552

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 943 AN: 68004

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.0109 Hom.: 26

Bravo AF: 0.00698

TwinsUK AF: 0.0154 AC: 57

ALSPAC AF: 0.0145 AC: 56

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0133 AC: 114

ExAC AF: 0.00929 AC: 1128

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.70
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.27
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.79	P
Vest4		0.041
MVP		0.67
MPC		0.26
ClinPred		0.047	T
GERP RS		2.0
Varity_R		0.12
gMVP		0.25
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17849952; hg19: chr12-71537951;