rs181166265

Variant names:

• chr8-80072800-T-C
• rs181166265
• NM_001025253.3:c.20-8207A>G

Variant summary

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

The NM_001025253.3(TPD52):​c.20-8207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 140,536 control chromosomes in the GnomAD database, including 298 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 0.053 (298 hom., cov: 31)
• Consequence: TPD52 NM_001025253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 3 publications found

Genes affected

TPD52 (HGNC:12005): (tumor protein D52) Enables calcium ion binding activity and protein homodimerization activity. Involved in B cell differentiation. Located in endoplasmic reticulum and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000276418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52	NM_001025253.3	c.20-8207A>G		intron_variant	Intron 1 of 7	ENST00000518937.6	NP_001020424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52	ENST00000518937.6	c.20-8207A>G		intron_variant	Intron 1 of 7	2	NM_001025253.3	ENSP00000429915.1
ENSG00000276418	ENST00000522938.5	n.139+7515A>G		intron_variant	Intron 1 of 7	2		ENSP00000430858.2

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 7490 AN: 140484 Hom.: 298 Cov.: 31

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0480

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

GnomAD4 genome AF: 0.0533 AC: 7488 AN: 140536 Hom.: 298 Cov.: 31 AF XY: 0.0537 AC XY: 3687 AN XY: 68644

African (AFR) AF: 0.0181 AC: 606 AN: 33488

American (AMR) AF: 0.0387 AC: 559 AN: 14428

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 98 AN: 3398

East Asian (EAS) AF: 0.0147 AC: 69 AN: 4698

South Asian (SAS) AF: 0.0418 AC: 191 AN: 4574

European-Finnish (FIN) AF: 0.0791 AC: 781 AN: 9876

Middle Eastern (MID) AF: 0.0140 AC: 4 AN: 286

European-Non Finnish (NFE) AF: 0.0733 AC: 4907 AN: 66934

Other (OTH) AF: 0.0476 AC: 93 AN: 1954

Alfa AF: 0.0591 Hom.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.20
PhyloP100		-1.7
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: rs181166265; hg19: chr8-80985035; COSMIC: COSV66951677;