Variant 7-130185200-C-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.943G>T(p.Ala315Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TMEM209
NM_032842.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

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:

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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
TMEM209	NM_032842.4 linkuse as main transcript	c.943G>T	p.Ala315Ser	missense_variant	7/15	ENST00000397622.7	NP_116231.2
TMEM209	NM_001363478.2 linkuse as main transcript	c.940G>T	p.Ala314Ser	missense_variant	7/15		NP_001350407.1
TMEM209	NM_001301163.2 linkuse as main transcript	c.943G>T	p.Ala315Ser	missense_variant	7/14		NP_001288092.1
TMEM209	NR_156699.2 linkuse as main transcript	n.974G>T		non_coding_transcript_exon_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM209	ENST00000397622.7 linkuse as main transcript	c.943G>T	p.Ala315Ser	missense_variant	7/15	1	NM_032842.4	ENSP00000380747	P4	Q96SK2-1
TMEM209	ENST00000473456.5 linkuse as main transcript	c.943G>T	p.Ala315Ser	missense_variant	7/14	1		ENSP00000417258		Q96SK2-3
	ENST00000483283.1 linkuse as main transcript	n.293+3467C>A		intron_variant, non_coding_transcript_variant		4
TMEM209	ENST00000462753.5 linkuse as main transcript	c.940G>T	p.Ala314Ser	missense_variant	7/15	5		ENSP00000419697	A1	Q96SK2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000478

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459100

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.000478

Bravo

AF:

0.00000756

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

Nov 13, 2023

The c.943G>T (p.A315S) alteration is located in exon 7 (coding exon 7) of the TMEM209 gene. This alteration results from a G to T substitution at nucleotide position 943, causing the alanine (A) at amino acid position 315 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0039

T;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.055

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.66

MutPred

0.65

Loss of helix (P = 0.0304);.;Loss of helix (P = 0.0304);

MVP

0.65

MPC

0.32

ClinPred

0.79

GERP RS

5.7

Varity_R

0.17

gMVP

0.47

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