Variant 12-10186497-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001384896.1(TMEM52B):c.215G>A(p.Arg72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000969 in 1,610,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 1 hom. )

Consequence

TMEM52B
NM_001384896.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.823

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039849877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM52B	NM_001384896.1 linkuse as main transcript	c.215G>A	p.Arg72His	missense_variant	4/5	ENST00000543484.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM52B	ENST00000543484.2 linkuse as main transcript	c.215G>A	p.Arg72His	missense_variant	4/5	4	NM_001384896.1	P1	Q4KMG9-1
TMEM52B	ENST00000298530.7 linkuse as main transcript	c.155G>A	p.Arg52His	missense_variant	3/4	1			Q4KMG9-2
TMEM52B	ENST00000381923.6 linkuse as main transcript	c.215G>A	p.Arg72His	missense_variant	5/6	5		P1	Q4KMG9-1
TMEM52B	ENST00000546153.1 linkuse as main transcript	n.101G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

250898

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000884

AC:

129

AN:

1458468

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

725656

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000177

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.155G>A (p.R52H) alteration is located in exon 3 (coding exon 3) of the TMEM52B gene. This alteration results from a G to A substitution at nucleotide position 155, causing the arginine (R) at amino acid position 52 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.042

T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.59

D;D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.060

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.035

B;B;.

Vest4

0.33

MVP

0.19

MPC

0.10

ClinPred

0.051

GERP RS

2.6

Varity_R

0.068

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over