Variant 9-68540571-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 13/20 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03357029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM252	NM_153237.2 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	1/2	ENST00000377311.4	NP_694969.1	Q8N6L7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM252	ENST00000377311.4 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	1/2	1	NM_153237.2	ENSP00000366528.4		Q8N6L7

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

GnomAD3 exomes

AF:

0.000355

AC:

AN:

250952

Hom.:

AF XY:

0.000398

AC XY:

AN XY:

135620

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000348

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000430

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

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 13, 2021

The c.244G>A (p.A82T) alteration is located in exon 1 (coding exon 1) of the TMEM252 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the alanine (A) at amino acid position 82 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

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

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

Varity_R

0.056

gMVP

0.21

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

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