Variant 9-68537443-T-G 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_153237.2(TMEM252):c.329A>C(p.Gln110Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,604,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

TMEM252
NM_153237.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065898806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM252	NM_153237.2 linkuse as main transcript	c.329A>C	p.Gln110Pro	missense_variant	2/2	ENST00000377311.4	NP_694969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM252	ENST00000377311.4 linkuse as main transcript	c.329A>C	p.Gln110Pro	missense_variant	2/2	1	NM_153237.2	ENSP00000366528	P1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00318

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000920

AC:

AN:

239084

Hom.:

AF XY:

0.0000695

AC XY:

AN XY:

129508

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.000345

GnomAD4 exome

AF:

0.000169

AC:

245

AN:

1452182

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

117

AN XY:

722380

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000356

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.000267

GnomAD4 genome

AF:

0.000105

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000115

AC:

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

Apr 05, 2023

The c.329A>C (p.Q110P) alteration is located in exon 2 (coding exon 2) of the TMEM252 gene. This alteration results from a A to C substitution at nucleotide position 329, causing the glutamine (Q) at amino acid position 110 to be replaced by a proline (P). 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

0.063

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.26

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.44

M_CAP

Benign

0.0041

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.10

Sift

Uncertain

0.010

Sift4G

Uncertain

0.011

Polyphen

0.023

Vest4

0.22

MVP

0.030

MPC

0.058

ClinPred

0.27

GERP RS

-0.59

Varity_R

0.47

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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