rs10516434

Variant names:

• chr4-98524164-C-T
• rs10516434
• NM_005723.4:c.82-16436G>A

Variant summary

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

The NM_005723.4(TSPAN5):​c.82-16436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,024 control chromosomes in the GnomAD database, including 3,529 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 0.21 (3529 hom., cov: 33)
• Consequence: TSPAN5 NM_005723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 2 publications found

Genes affected

TSPAN5 (HGNC:17753): (tetraspanin 5) 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. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN5	NM_005723.4	c.82-16436G>A		intron_variant	Intron 1 of 7	ENST00000305798.8	NP_005714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN5	ENST00000305798.8	c.82-16436G>A		intron_variant	Intron 1 of 7	1	NM_005723.4	ENSP00000307701.3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32095 AN: 151906 Hom.: 3525 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.211 AC: 32117 AN: 152024 Hom.: 3529 Cov.: 33 AF XY: 0.206 AC XY: 15275 AN XY: 74308

African (AFR) AF: 0.231 AC: 9549 AN: 41426

American (AMR) AF: 0.176 AC: 2685 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3464

East Asian (EAS) AF: 0.0940 AC: 487 AN: 5180

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10558

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14850 AN: 67986

Other (OTH) AF: 0.225 AC: 472 AN: 2102

Alfa AF: 0.213 Hom.: 575

Bravo AF: 0.210

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.069
DANN	Benign	0.46
PhyloP100		-3.1
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: rs10516434; hg19: chr4-99445315;