chr12-71139754-C-G

Variant names:

• chr12-71139754-C-G
• rs3763978
• NM_004616.3:c.218G>C

Variant summary

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

The NM_004616.3(TSPAN8):​c.218G>C​(p.Gly73Ala) variant causes a missense change. The variant allele was found at a frequency of 0.373 in 1,612,202 control chromosomes in the GnomAD database, including 118,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7969 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110187 hom.)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 45 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=0.0057137907).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.218G>C	p.Gly73Ala	missense	Exon 4 of 9	NP_004607.1
	TSPAN8	NM_001369760.1		c.218G>C	p.Gly73Ala	missense	Exon 3 of 8	NP_001356689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.218G>C	p.Gly73Ala	missense	Exon 4 of 9	ENSP00000247829.3
	TSPAN8	ENST00000393330.6	TSL:1	c.218G>C	p.Gly73Ala	missense	Exon 7 of 12	ENSP00000377003.2
	TSPAN8	ENST00000546561.2	TSL:1	c.218G>C	p.Gly73Ala	missense	Exon 3 of 8	ENSP00000447160.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44603 AN: 151926 Hom.: 7967 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.329 AC: 82526 AN: 250554 AF XY: 0.342

Gnomad AFR exome AF: 0.0854

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.381 AC: 556859 AN: 1460158 Hom.: 110187 Cov.: 41 AF XY: 0.381 AC XY: 276909 AN XY: 726328

African (AFR) AF: 0.0820 AC: 2744 AN: 33452

American (AMR) AF: 0.186 AC: 8293 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 11036 AN: 26090

East Asian (EAS) AF: 0.311 AC: 12325 AN: 39650

South Asian (SAS) AF: 0.291 AC: 25001 AN: 86000

European-Finnish (FIN) AF: 0.354 AC: 18898 AN: 53344

Middle Eastern (MID) AF: 0.383 AC: 2205 AN: 5756

European-Non Finnish (NFE) AF: 0.409 AC: 454653 AN: 1110890

Other (OTH) AF: 0.360 AC: 21704 AN: 60310

GnomAD4 genome AF: 0.293 AC: 44601 AN: 152044 Hom.: 7969 Cov.: 32 AF XY: 0.290 AC XY: 21544 AN XY: 74326

African (AFR) AF: 0.0923 AC: 3833 AN: 41524

American (AMR) AF: 0.249 AC: 3801 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1486 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1569 AN: 5160

South Asian (SAS) AF: 0.279 AC: 1341 AN: 4808

European-Finnish (FIN) AF: 0.336 AC: 3554 AN: 10564

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27756 AN: 67952

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.379 Hom.: 3840

Bravo AF: 0.280

TwinsUK AF: 0.410 AC: 1521

ALSPAC AF: 0.418 AC: 1612

ESP6500AA AF: 0.110 AC: 483

ESP6500EA AF: 0.410 AC: 3526

ExAC AF: 0.333 AC: 40448

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.7	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.67
Sift	Benign	0.033	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.26
MPC		0.47
ClinPred		0.055	T
GERP RS		5.1
Varity_R		0.72
gMVP		0.93
Mutation Taster		=95/5	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: rs3763978; hg19: chr12-71533534; COSMIC: COSV56077446; COSMIC: COSV56077446;