8-80138778-C-T

Variant names:

• chr8-80138778-C-T
• rs2162229
• NM_001025253.3:c.19+32647G>A

Variant summary

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

The NM_001025253.3(TPD52):​c.19+32647G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,912 control chromosomes in the GnomAD database, including 18,215 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 0.49 (18215 hom., cov: 31)
• Consequence: TPD52 NM_001025253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 6 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]

TPD52-MRPS28 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025253.3. 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
	TPD52	NM_001025253.3	MANE Select	c.19+32647G>A		intron	N/A	NP_001020424.1
	TPD52-MRPS28	NM_001387778.1		c.19+32647G>A		intron	N/A	NP_001374707.1
	TPD52	NM_005079.4		c.19+32647G>A		intron	N/A	NP_005070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52	ENST00000518937.6	TSL:2 MANE Select	c.19+32647G>A		intron	N/A	ENSP00000429915.1
	TPD52	ENST00000379096.9	TSL:1	c.19+32647G>A		intron	N/A	ENSP00000368390.4
	TPD52	ENST00000519303.6	TSL:1	c.-423+32243G>A		intron	N/A	ENSP00000428951.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73778 AN: 151794 Hom.: 18203 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.486 AC: 73829 AN: 151912 Hom.: 18215 Cov.: 31 AF XY: 0.487 AC XY: 36164 AN XY: 74222

African (AFR) AF: 0.526 AC: 21808 AN: 41430

American (AMR) AF: 0.515 AC: 7869 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3466

East Asian (EAS) AF: 0.763 AC: 3932 AN: 5156

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4816

European-Finnish (FIN) AF: 0.481 AC: 5073 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29714 AN: 67932

Other (OTH) AF: 0.495 AC: 1042 AN: 2106

Alfa AF: 0.461 Hom.: 3907

Bravo AF: 0.496

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.69
PhyloP100		-0.75
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2162229; hg19: chr8-81051013;