Variant 7-130192739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032842.4(TMEM209):c.658C>T(p.Arg220Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TMEM209
NM_032842.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36

Variant links:

Genes affected

TMEM209 (HGNC:21898): (transmembrane protein 209) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM209 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM209	NM_032842.4 linkuse as main transcript	c.658C>T	p.Arg220Cys	missense_variant	6/15	ENST00000397622.7	NP_116231.2
LOC124901745	XR_007060521.1 linkuse as main transcript	n.233+427G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM209	ENST00000397622.7 linkuse as main transcript	c.658C>T	p.Arg220Cys	missense_variant	6/15	1	NM_032842.4	ENSP00000380747	P4	Q96SK2-1
TMEM209	ENST00000473456.5 linkuse as main transcript	c.658C>T	p.Arg220Cys	missense_variant	6/14	1		ENSP00000417258		Q96SK2-3
	ENST00000483283.1 linkuse as main transcript	n.352+427G>A		intron_variant, non_coding_transcript_variant		4
TMEM209	ENST00000462753.5 linkuse as main transcript	c.655C>T	p.Arg219Cys	missense_variant	6/15	5		ENSP00000419697	A1	Q96SK2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000722

AC:

AN:

249144

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000521

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000497

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

Jun 10, 2022

The c.658C>T (p.R220C) alteration is located in exon 6 (coding exon 6) of the TMEM209 gene. This alteration results from a C to T substitution at nucleotide position 658, causing the arginine (R) at amino acid position 220 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

T;.;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.3

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

D;D;N

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.82

MutPred

0.64

Loss of methylation at R220 (P = 0.0093);.;Loss of methylation at R220 (P = 0.0093);

MVP

0.55

MPC

0.15

ClinPred

0.49

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.51

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