dbSNP rs1324285788: TMEM219:p.Asn9Ser (chr16-29963169-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001083613.2(TMEM219):c.26A>G(p.Asn9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N9I) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM219
NM_001083613.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26

Publications

0 publications found

Variant links:

Genes affected

TMEM219 (HGNC:25201): (transmembrane protein 219) Predicted to be involved in apoptotic process. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM219 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28337574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM219	NM_001083613.2 link	c.26A>G	p.Asn9Ser	missense_variant	Exon 2 of 6	ENST00000279396.11	NP_001077082.1	Q86XT9A0A024R618

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM219	ENST00000279396.11 link	c.26A>G	p.Asn9Ser	missense_variant	Exon 2 of 6	1	NM_001083613.2	ENSP00000279396.6		Q86XT9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;T;T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.73

.;.;T;T;.;.

M_CAP

Benign

0.0033

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.81

L;.;L;.;L;L

PhyloP100

4.3

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

D;.;D;.;D;D

REVEL

Benign

0.14

Sift

Benign

0.080

T;.;T;.;T;T

Sift4G

Benign

0.062

T;T;T;T;T;T

Polyphen

0.59

P;.;P;.;P;P

Vest4

0.61

MutPred

0.40

Gain of glycosylation at N9 (P = 0.0709);Gain of glycosylation at N9 (P = 0.0709);Gain of glycosylation at N9 (P = 0.0709);Gain of glycosylation at N9 (P = 0.0709);Gain of glycosylation at N9 (P = 0.0709);Gain of glycosylation at N9 (P = 0.0709);

MVP

0.37

MPC

0.37

ClinPred

0.95

GERP RS

5.7

PromoterAI

-0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.77

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over