Variant 11-60922050-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024092.3(TMEM109):c.617G>A(p.Arg206Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,612,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

TMEM109
NM_024092.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

TMEM109 (HGNC:28771): (transmembrane protein 109) Predicted to enable voltage-gated ion channel activity. Acts upstream of or within cellular response to gamma radiation and negative regulation of cell death. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM109 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1567778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM109	NM_024092.3 linkuse as main transcript	c.617G>A	p.Arg206Gln	missense_variant	4/4	ENST00000227525.8	NP_076997.1
LOC124902676	XR_007062688.1 linkuse as main transcript	n.180-2897C>T		intron_variant, non_coding_transcript_variant
LOC124902676	XR_007062689.1 linkuse as main transcript	n.103+2244C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM109	ENST00000227525.8 linkuse as main transcript	c.617G>A	p.Arg206Gln	missense_variant	4/4	1	NM_024092.3	ENSP00000227525	P1
	ENST00000543907.2 linkuse as main transcript	n.180-2897C>T		intron_variant, non_coding_transcript_variant		3
TMEM109	ENST00000536171.1 linkuse as main transcript	c.617G>A	p.Arg206Gln	missense_variant	3/3	2		ENSP00000443990	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000648

AC:

AN:

247074

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134256

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.0000806

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000815

AC:

119

AN:

1460676

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000191

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000861

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000661

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Feb 17, 2022

The c.617G>A (p.R206Q) alteration is located in exon 4 (coding exon 3) of the TMEM109 gene. This alteration results from a G to A substitution at nucleotide position 617, causing the arginine (R) at amino acid position 206 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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

0.032

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.052

Sift

Benign

0.25

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.99

D;D

Vest4

0.069

MVP

0.35

MPC

1.0

ClinPred

0.13

GERP RS

4.9

Varity_R

0.040

gMVP

0.19

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