Genetic Variant TMEM52B:p.Thr61Met (chr12-10186464-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001384896.1(TMEM52B):c.182C>T(p.Thr61Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000383 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TMEM52B
NM_001384896.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.728

Publications

0 publications found

Variant links:

Genes affected

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

TMEM52B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1616306).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM52B	NM_001384896.1	MANE Select	c.182C>T	p.Thr61Met	missense	Exon 4 of 5	NP_001371825.1	Q4KMG9-1
TMEM52B	NM_001079815.2		c.182C>T	p.Thr61Met	missense	Exon 5 of 6	NP_001073283.1	Q4KMG9-1
TMEM52B	NM_001384894.1		c.182C>T	p.Thr61Met	missense	Exon 7 of 8	NP_001371823.1	Q4KMG9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM52B	ENST00000543484.2	TSL:4 MANE Select	c.182C>T	p.Thr61Met	missense	Exon 4 of 5	ENSP00000445582.2	Q4KMG9-1
TMEM52B	ENST00000298530.7	TSL:1	c.122C>T	p.Thr41Met	missense	Exon 3 of 4	ENSP00000298530.3	Q4KMG9-2
TMEM52B	ENST00000381923.6	TSL:5	c.182C>T	p.Thr61Met	missense	Exon 5 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000677

AC:

AN:

251156

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1460266

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.000101

AC:

AN:

39690

South Asian (SAS)

AF:

0.000232

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1110750

Other (OTH)

AF:

0.0000995

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.076

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.7

PhyloP100

0.73

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.15

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.82

Vest4

0.60

MutPred

0.35

Gain of catalytic residue at S62 (P = 0)

MVP

0.36

MPC

0.32

ClinPred

0.28

GERP RS

3.6

Varity_R

0.12

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over