chr12-10186464-C-A

Variant names:

• chr12-10186464-C-A
• rs753748877
• NM_001384896.1:c.182C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384896.1(TMEM52B):​c.182C>A​(p.Thr61Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. T61M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM52B NM_001384896.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22003546).

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.182C>A	p.Thr61Lys	missense	Exon 4 of 5	NP_001371825.1	Q4KMG9-1
	TMEM52B	NM_001079815.2		c.182C>A	p.Thr61Lys	missense	Exon 5 of 6	NP_001073283.1	Q4KMG9-1
	TMEM52B	NM_001384894.1		c.182C>A	p.Thr61Lys	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.182C>A	p.Thr61Lys	missense	Exon 4 of 5	ENSP00000445582.2	Q4KMG9-1
	TMEM52B	ENST00000298530.7	TSL:1	c.122C>A	p.Thr41Lys	missense	Exon 3 of 4	ENSP00000298530.3	Q4KMG9-2
	TMEM52B	ENST00000381923.6	TSL:5	c.182C>A	p.Thr61Lys	missense	Exon 5 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.73
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.50	P
Vest4		0.65
MutPred		0.38		Gain of catalytic residue at T61 (P = 0.0014)
MVP		0.26
MPC		0.39
ClinPred		0.90	D
GERP RS		3.6
Varity_R		0.32
gMVP		0.71
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs753748877; hg19: chr12-10339063;