Genetic Variant NM_001083613.2:c.203C>A (chr16-29963437-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083613.2(TMEM219):c.203C>A(p.Thr68Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TMEM219
NM_001083613.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.516

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25164348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083613.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM219	NM_001083613.2	MANE Select	c.203C>A	p.Thr68Asn	missense	Exon 3 of 6	NP_001077082.1	Q86XT9
TMEM219	NM_001369688.1		c.203C>A	p.Thr68Asn	missense	Exon 2 of 5	NP_001356617.1	Q86XT9
TMEM219	NM_194280.4		c.203C>A	p.Thr68Asn	missense	Exon 3 of 6	NP_919256.1	Q86XT9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM219	ENST00000279396.11	TSL:1 MANE Select	c.203C>A	p.Thr68Asn	missense	Exon 3 of 6	ENSP00000279396.6	Q86XT9
TMEM219	ENST00000414689.6	TSL:1	c.203C>A	p.Thr68Asn	missense	Exon 3 of 6	ENSP00000388485.2	Q86XT9
TMEM219	ENST00000566848.5	TSL:1	c.203C>A	p.Thr68Asn	missense	Exon 2 of 5	ENSP00000457492.1	Q86XT9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249330

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

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:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.034

Eigen

Benign

0.033

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.59

M_CAP

Benign

0.0014

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.52

PrimateAI

Benign

0.43

PROVEAN

Benign

0.11

REVEL

Benign

0.23

Sift

Benign

0.42

Sift4G

Uncertain

0.016

Polyphen

0.72

Vest4

0.28

MutPred

0.33

Loss of sheet (P = 0.0181)

MVP

0.16

MPC

0.26

ClinPred

0.16

GERP RS

3.9

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.22

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over