Variant 20-2816566-G-T 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_001167670.3(TMEM239):c.12G>T(p.Gln4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,369,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

TMEM239
NM_001167670.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

TMEM239 (HGNC:40044): (transmembrane protein 239) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM239 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=0.014738977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM239	NM_001167670.3 linkuse as main transcript	c.12G>T	p.Gln4His	missense_variant	2/2	ENST00000380585.2	NP_001161142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM239	ENST00000380585.2 linkuse as main transcript	c.12G>T	p.Gln4His	missense_variant	2/2	1	NM_001167670.3	ENSP00000369959	P1	Q8WW34-2
TMEM239	ENST00000361033.1 linkuse as main transcript	c.141G>T	p.Gln47His	missense_variant	2/2	2		ENSP00000354312		Q8WW34-1

Frequencies

GnomAD3 genomes

AF:

0.000422

AC:

AN:

142308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000767

Gnomad AMI

AF:

0.00569

Gnomad AMR

AF:

0.0000709

Gnomad ASJ

AF:

0.00237

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000641

Gnomad OTH

AF:

0.000504

GnomAD3 exomes

AF:

0.000361

AC:

AN:

138654

Hom.:

AF XY:

0.000360

AC XY:

AN XY:

74976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000815

Gnomad ASJ exome

AF:

0.000955

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000668

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.000439

AC:

539

AN:

1227484

Hom.:

Cov.:

AF XY:

0.000455

AC XY:

275

AN XY:

604078

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000637

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000257

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000502

Gnomad4 OTH exome

AF:

0.000380

GnomAD4 genome

AF:

0.000421

AC:

AN:

142430

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

AN XY:

68934

show subpopulations

Gnomad4 AFR

AF:

0.0000765

Gnomad4 AMR

AF:

0.0000708

Gnomad4 ASJ

AF:

0.00237

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000641

Gnomad4 OTH

AF:

0.000499

Alfa

AF:

0.000359

Hom.:

Bravo

AF:

0.000400

ExAC

AF:

0.000187

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

Oct 26, 2021

The c.12G>T (p.Q4H) alteration is located in exon 2 (coding exon 1) of the TMEM239 gene. This alteration results from a G to T substitution at nucleotide position 12, causing the glutamine (Q) at amino acid position 4 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.24

M_CAP

Benign

0.025

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.94

N;N;N

PROVEAN

Benign

0.58

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Vest4

0.26

MVP

0.030

ClinPred

0.24

GERP RS

4.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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