Genetic Variant TMEM252:p.Ala82Thr (chr9-68540571-C-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_153237.2(TMEM252):c.244G>A(p.Ala82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,614,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

TMEM252
NM_153237.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525

Publications

4 publications found

Variant links:

Genes affected

TMEM252 (HGNC:28537): (transmembrane protein 252) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM252 links:

LINC01506 (HGNC:51187): (long intergenic non-protein coding RNA 1506)

LINC01506 links:

TMEM252-DT (HGNC:54377): (TMEM252 divergent transcript)

TMEM252-DT 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=0.03357029).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153237.2. 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
	TMEM252	NM_153237.2	MANE Select	c.244G>A	p.Ala82Thr	missense	Exon 1 of 2	NP_694969.1	Q8N6L7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM252	ENST00000377311.4	TSL:1 MANE Select	c.244G>A	p.Ala82Thr	missense	Exon 1 of 2	ENSP00000366528.4	Q8N6L7
LINC01506	ENST00000762445.1		n.217+4930G>A		intron	N/A
LINC01506	ENST00000762446.1		n.200+4930G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000355

AC:

AN:

250952

AF XY:

0.000398

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000600

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000482

AC:

704

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

341

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000584

AC:

649

AN:

1111988

Other (OTH)

AF:

0.000464

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.000348

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41574

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68028

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000447

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000593

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

0.088

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.71

M_CAP

Benign

0.0072

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.53

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.032

Sift

Benign

0.085

Sift4G

Benign

0.38

Polyphen

0.78

Vest4

0.21

MVP

0.048

MPC

0.20

ClinPred

0.040

GERP RS

2.7

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.056

gMVP

0.21

Mutation Taster

=95/5

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

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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