8-80119587-A-G

Variant names:

• chr8-80119587-A-G
• rs10957961
• NM_001025253.3:c.19+51838T>C

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+51838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,084 control chromosomes in the GnomAD database, including 33,444 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 0.65 (33444 hom., cov: 32)
• Consequence: TPD52 NM_001025253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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+51838T>C		intron	N/A	NP_001020424.1
	TPD52-MRPS28	NM_001387778.1		c.19+51838T>C		intron	N/A	NP_001374707.1
	TPD52	NM_005079.4		c.19+51838T>C		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+51838T>C		intron	N/A	ENSP00000429915.1
	TPD52	ENST00000379096.9	TSL:1	c.19+51838T>C		intron	N/A	ENSP00000368390.4
	TPD52	ENST00000519303.6	TSL:1	c.-423+51434T>C		intron	N/A	ENSP00000428951.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98327 AN: 151966 Hom.: 33402 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.647 AC: 98428 AN: 152084 Hom.: 33444 Cov.: 32 AF XY: 0.646 AC XY: 48062 AN XY: 74350

African (AFR) AF: 0.865 AC: 35931 AN: 41518

American (AMR) AF: 0.636 AC: 9723 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4059 AN: 5172

South Asian (SAS) AF: 0.618 AC: 2973 AN: 4812

European-Finnish (FIN) AF: 0.530 AC: 5595 AN: 10558

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35865 AN: 67960

Other (OTH) AF: 0.653 AC: 1376 AN: 2108

Alfa AF: 0.604 Hom.: 8264

Bravo AF: 0.666

Asia WGS AF: 0.711 AC: 2468 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10957961; hg19: chr8-81031822;