Variant 17-10729815-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004313.3(TMEM220):c.37A>T(p.Met13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000426 in 1,406,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

TMEM220
NM_001004313.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

TMEM220 (HGNC:33757): (transmembrane protein 220) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM220 links:

TMEM220-AS1 (HGNC:44357): (TMEM220 antisense RNA 1)

TMEM220-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3612992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM220	NM_001004313.3 linkuse as main transcript	c.37A>T	p.Met13Leu	missense_variant	1/6	ENST00000341871.8	NP_001004313.1
TMEM220-AS1	NR_073458.1 linkuse as main transcript	n.39T>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM220	ENST00000341871.8 linkuse as main transcript	c.37A>T	p.Met13Leu	missense_variant	1/6	1	NM_001004313.3	ENSP00000339830	P1	Q6QAJ8-1
TMEM220-AS1	ENST00000580899.1 linkuse as main transcript	n.20T>A		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000729

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:

0.00

GnomAD4 exome

AF:

0.00000239

AC:

AN:

1255146

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

610058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000350

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000199

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0000729

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:

0.00

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

Jun 22, 2021

The c.37A>T (p.M13L) alteration is located in exon 1 (coding exon 1) of the TMEM220 gene. This alteration results from a A to T substitution at nucleotide position 37, causing the methionine (M) at amino acid position 13 to be replaced by a leucine (L). 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

Uncertain

0.50

BayesDel_addAF

Benign

0.0081

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.78

DEOGEN2

Benign

0.023

T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.74

T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.20

Sift

Uncertain

0.023

D;D;.

Sift4G

Uncertain

0.040

D;T;D

Polyphen

0.80

P;P;.

Vest4

0.53

MutPred

0.45

Loss of MoRF binding (P = 0.1531);Loss of MoRF binding (P = 0.1531);Loss of MoRF binding (P = 0.1531);

MVP

0.12

MPC

1.1

ClinPred

0.80

GERP RS

3.8

Varity_R

0.47

gMVP

0.30

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