NM_004616.3:c.444+2242C>T

Variant names:

• chr12-71135711-G-A
• rs10506626
• NM_004616.3:c.444+2242C>T

Variant summary

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

The NM_004616.3(TSPAN8):​c.444+2242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,958 control chromosomes in the GnomAD database, including 8,557 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 0.32 (8557 hom., cov: 30)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 9 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 (BayesDel_noAF=-0.83).
• 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.444+2242C>T		intron	N/A	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.444+2242C>T		intron	N/A	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.444+2242C>T		intron	N/A	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.444+2242C>T		intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.444+2242C>T		intron	N/A	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48476 AN: 151840 Hom.: 8553 Cov.: 30

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48495 AN: 151958 Hom.: 8557 Cov.: 30 AF XY: 0.314 AC XY: 23319 AN XY: 74230

African (AFR) AF: 0.178 AC: 7371 AN: 41476

American (AMR) AF: 0.259 AC: 3952 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3462

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5160

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4820

European-Finnish (FIN) AF: 0.340 AC: 3582 AN: 10532

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27810 AN: 67934

Other (OTH) AF: 0.343 AC: 721 AN: 2104

Alfa AF: 0.336 Hom.: 1616

Bravo AF: 0.308

Asia WGS AF: 0.262 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		0.14
Mutation Taster		=100/0	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: rs10506626; hg19: chr12-71529491;