12-10186539-T-A

Variant names:

• chr12-10186539-T-A
• rs1948881727
• NM_001384896.1:c.257T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001384896.1(TMEM52B):​c.257T>A​(p.Val86Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM52B NM_001384896.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

TMEM52B (HGNC:26438): (transmembrane protein 52B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384896.1. 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
	TMEM52B	NM_001384896.1	MANE Select	c.257T>A	p.Val86Glu	missense	Exon 4 of 5	NP_001371825.1	Q4KMG9-1
	TMEM52B	NM_001079815.2		c.257T>A	p.Val86Glu	missense	Exon 5 of 6	NP_001073283.1	Q4KMG9-1
	TMEM52B	NM_001384894.1		c.257T>A	p.Val86Glu	missense	Exon 7 of 8	NP_001371823.1	Q4KMG9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM52B	ENST00000543484.2	TSL:4 MANE Select	c.257T>A	p.Val86Glu	missense	Exon 4 of 5	ENSP00000445582.2	Q4KMG9-1
	TMEM52B	ENST00000298530.7	TSL:1	c.197T>A	p.Val66Glu	missense	Exon 3 of 4	ENSP00000298530.3	Q4KMG9-2
	TMEM52B	ENST00000381923.6	TSL:5	c.257T>A	p.Val86Glu	missense	Exon 5 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.55		Gain of catalytic residue at P83 (P = 0)
MVP		0.65
MPC		0.57
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.83
gMVP		0.82
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1948881727; hg19: chr12-10339138;