Variant 20-2816571-G-A 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.17G>A(p.Arg6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 1,510,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

TMEM239
NM_001167670.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.414

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=0.05854255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM239	NM_001167670.3 linkuse as main transcript	c.17G>A	p.Arg6Gln	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.17G>A	p.Arg6Gln	missense_variant	2/2	1	NM_001167670.3	ENSP00000369959	P1	Q8WW34-2
TMEM239	ENST00000361033.1 linkuse as main transcript	c.146G>A	p.Arg49Gln	missense_variant	2/2	2		ENSP00000354312		Q8WW34-1

Frequencies

GnomAD3 genomes

AF:

0.0000673

AC:

AN:

148692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

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:

0.00

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

139140

Hom.:

AF XY:

0.0000266

AC XY:

AN XY:

75148

show subpopulations

Gnomad AFR exome

AF:

0.000271

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000426

AC:

AN:

1362298

Hom.:

Cov.:

AF XY:

0.0000342

AC XY:

AN XY:

672190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000964

Gnomad4 AMR exome

AF:

0.0000854

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000451

Gnomad4 OTH exome

AF:

0.0000532

GnomAD4 genome

AF:

0.0000673

AC:

AN:

148692

Hom.:

Cov.:

AF XY:

0.0000967

AC XY:

AN XY:

72388

show subpopulations

Gnomad4 AFR

AF:

0.000172

Gnomad4 AMR

AF:

0.000134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000485

Bravo

AF:

0.000125

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

Sep 14, 2021

The c.17G>A (p.R6Q) alteration is located in exon 2 (coding exon 1) of the TMEM239 gene. This alteration results from a G to A substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a glutamine (Q). 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

0.084

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.73

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.092

Sift

Benign

0.090

T;T

Sift4G

Benign

0.16

T;T

Vest4

0.095

MVP

0.014

ClinPred

0.088

GERP RS

3.7

Varity_R

0.11

gMVP

0.081

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