Genetic Variant TMEM52B:p.Ala9Ser (chr12-10179599-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384896.1(TMEM52B):c.25G>T(p.Ala9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

TMEM52B
NM_001384896.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.495

Publications

2 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015441507).

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.25G>T	p.Ala9Ser	missense	Exon 1 of 5	NP_001371825.1	Q4KMG9-1
TMEM52B	NM_001079815.2		c.25G>T	p.Ala9Ser	missense	Exon 2 of 6	NP_001073283.1	Q4KMG9-1
TMEM52B	NM_001384894.1		c.25G>T	p.Ala9Ser	missense	Exon 4 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.25G>T	p.Ala9Ser	missense	Exon 1 of 5	ENSP00000445582.2	Q4KMG9-1
TMEM52B	ENST00000298530.7	TSL:1	c.9G>T	p.Trp3Cys	missense	Exon 1 of 4	ENSP00000298530.3	Q4KMG9-2
TMEM52B	ENST00000381923.6	TSL:5	c.25G>T	p.Ala9Ser	missense	Exon 2 of 6	ENSP00000371348.2	Q4KMG9-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000374

AC:

AN:

251476

AF XY:

0.000412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

209

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000568

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000936

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000234

AC:

260

AN:

1111998

Other (OTH)

AF:

0.000381

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

104

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:

0.000223

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41568

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.000296

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.000711

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

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0070

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.24

M_CAP

Benign

0.0020

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

PhyloP100

-0.49

PROVEAN

Benign

0.40

REVEL

Benign

0.056

Sift

Benign

0.13

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.071

MVP

0.040

ClinPred

0.027

GERP RS

-5.3

Varity_R

0.044

gMVP

0.29

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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