rs10516433

Variant names:

• chr4-98522375-C-T
• rs10516433
• NM_005723.4:c.82-14647G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005723.4(TSPAN5):​c.82-14647G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,076 control chromosomes in the GnomAD database, including 3,553 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 (3553 hom., cov: 33)
• Consequence: TSPAN5 NM_005723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN5	NM_005723.4	c.82-14647G>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.82-14647G>A		intron_variant	Intron 1 of 7	1	NM_005723.4	ENSP00000307701.3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32200 AN: 151958 Hom.: 3549 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.212 AC: 32222 AN: 152076 Hom.: 3553 Cov.: 33 AF XY: 0.206 AC XY: 15309 AN XY: 74336

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.225

Alfa AF: 0.215 Hom.: 446

Bravo AF: 0.211

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516433; hg19: chr4-99443526;