8-80038168-G-C

Variant names:

• chr8-80038168-G-C
• rs534297357
• NM_001025253.3:c.572C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001025253.3(TPD52):​c.572C>G​(p.Ala191Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A191V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPD52 NM_001025253.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.35
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32766283).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52	NM_001025253.3	MANE Select	c.572C>G	p.Ala191Gly	missense	Exon 8 of 8	NP_001020424.1	P55327-4
	TPD52	NM_001287140.2		c.692C>G	p.Ala231Gly	missense	Exon 8 of 8	NP_001274069.1	P55327-6
	TPD52	NM_001287142.2		c.665C>G	p.Ala222Gly	missense	Exon 7 of 7	NP_001274071.1	P55327-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52	ENST00000518937.6	TSL:2 MANE Select	c.572C>G	p.Ala191Gly	missense	Exon 8 of 8	ENSP00000429915.1	P55327-4
	TPD52	ENST00000520527.5	TSL:1	c.692C>G	p.Ala231Gly	missense	Exon 8 of 8	ENSP00000429309.1	P55327-6
	TPD52	ENST00000448733.3	TSL:1	c.665C>G	p.Ala222Gly	missense	Exon 7 of 7	ENSP00000410222.2	P55327-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.24
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.49		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.66
MPC		0.91
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.29
Mutation Taster		=72/28	polymorphism

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: rs534297357; hg19: chr8-80950403;