Genetic Variant TMEM52:p.Ala48Val (chr1-1918920-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178545.4(TMEM52):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,391,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TMEM52
NM_178545.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Publications

0 publications found

Variant links:

Genes affected

TMEM52 (HGNC:27916): (transmembrane protein 52) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM52 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019704103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178545.4. 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
	TMEM52	NM_178545.4	MANE Select	c.143C>T	p.Ala48Val	missense	Exon 3 of 5	NP_848640.1	Q8NDY8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM52	ENST00000310991.8	TSL:1 MANE Select	c.143C>T	p.Ala48Val	missense	Exon 3 of 5	ENSP00000311122.3	Q8NDY8-1
TMEM52	ENST00000902364.1		c.161C>T	p.Ala54Val	missense	Exon 3 of 5	ENSP00000572423.1
TMEM52	ENST00000378598.4	TSL:5	c.229C>T	p.Pro77Ser	missense	Exon 2 of 3	ENSP00000367861.3	B1AKR2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000495

AC:

AN:

20196

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00463

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1239358

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

600688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24098

American (AMR)

AF:

0.00

AC:

AN:

12914

Ashkenazi Jewish (ASJ)

AF:

0.00108

AC:

AN:

17514

East Asian (EAS)

AF:

0.00

AC:

AN:

29562

South Asian (SAS)

AF:

0.00

AC:

AN:

54822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3598

European-Non Finnish (NFE)

AF:

0.00000788

AC:

AN:

1015838

Other (OTH)

AF:

0.000176

AC:

AN:

51188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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

AF:

0.0000329

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000449

AC:

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

0.27

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Benign

0.097

Eigen_PC

Benign

0.093

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

PhyloP100

2.6

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Uncertain

0.019

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.37

MutPred

0.22

Loss of relative solvent accessibility (P = 0.0676)

MVP

0.17

MPC

3.1

ClinPred

0.56

GERP RS

2.3

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.24

gMVP

0.23

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over