rs1051334

Variant names:

• chr12-71129354-A-C
• rs1051334
• NM_004616.3:c.637T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004616.3(TSPAN8):​c.637T>G​(p.Ser213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,572,296 control chromosomes in the GnomAD database, including 115,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8469 hom., cov: 31)
  • Exomes 𝑓: 0.38 (107226 hom.)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 47 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029125214).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

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.637T>G	p.Ser213Ala	missense	Exon 8 of 9	NP_004607.1
	TSPAN8	NM_001369760.1		c.637T>G	p.Ser213Ala	missense	Exon 7 of 8	NP_001356689.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.637T>G	p.Ser213Ala	missense	Exon 8 of 9	ENSP00000247829.3
	TSPAN8	ENST00000393330.6	TSL:1	c.637T>G	p.Ser213Ala	missense	Exon 11 of 12	ENSP00000377003.2
	TSPAN8	ENST00000546561.2	TSL:1	c.637T>G	p.Ser213Ala	missense	Exon 7 of 8	ENSP00000447160.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 47910 AN: 150822 Hom.: 8464 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.336 AC: 76898 AN: 229084 AF XY: 0.347

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.381 AC: 542199 AN: 1421378 Hom.: 107226 Cov.: 33 AF XY: 0.381 AC XY: 269447 AN XY: 706896

African (AFR) AF: 0.162 AC: 5140 AN: 31704

American (AMR) AF: 0.186 AC: 7528 AN: 40452

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11037 AN: 25378

East Asian (EAS) AF: 0.308 AC: 11882 AN: 38554

South Asian (SAS) AF: 0.289 AC: 23282 AN: 80566

European-Finnish (FIN) AF: 0.354 AC: 18658 AN: 52650

Middle Eastern (MID) AF: 0.392 AC: 2208 AN: 5630

European-Non Finnish (NFE) AF: 0.406 AC: 441107 AN: 1087640

Other (OTH) AF: 0.363 AC: 21357 AN: 58804

GnomAD4 genome AF: 0.318 AC: 47922 AN: 150918 Hom.: 8469 Cov.: 31 AF XY: 0.313 AC XY: 23018 AN XY: 73636

African (AFR) AF: 0.174 AC: 7173 AN: 41246

American (AMR) AF: 0.259 AC: 3949 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1571 AN: 5154

South Asian (SAS) AF: 0.279 AC: 1340 AN: 4798

European-Finnish (FIN) AF: 0.333 AC: 3333 AN: 10020

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.409 AC: 27714 AN: 67722

Other (OTH) AF: 0.342 AC: 715 AN: 2092

Alfa AF: 0.387 Hom.: 41968

Bravo AF: 0.307

TwinsUK AF: 0.413 AC: 1531

ALSPAC AF: 0.419 AC: 1614

ESP6500AA AF: 0.189 AC: 832

ESP6500EA AF: 0.410 AC: 3526

ExAC AF: 0.341 AC: 41401

Asia WGS AF: 0.260 AC: 900 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.36
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.8	N
PhyloP100		1.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.072
ClinPred		0.0023	T
GERP RS		4.9
Varity_R		0.11
gMVP		0.72
Mutation Taster		=99/1	polymorphism (auto)

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: rs1051334; hg19: chr12-71523134; COSMIC: COSV56081147;