Variant 19-17436805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190844.2(TMEM221):c.529C>T(p.Arg177Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000043 in 1,510,968 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 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TMEM221
NM_001190844.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

TMEM221 (HGNC:21943): (transmembrane protein 221) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM221 links:

ENSG00000269035 (HGNC:):

ENSG00000269035 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08143842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM221	NM_001190844.2 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	3/3	ENST00000341130.6	NP_001177773.1	A6NGB7
TMEM221	XM_011527603.3 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	3/4		XP_011525905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM221	ENST00000341130.6 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	3/3	2	NM_001190844.2	ENSP00000342162.5		A6NGB7
ENSG00000269035	ENST00000594663.1 linkuse as main transcript	c.484C>T	p.Arg162Trp	missense_variant	4/4	3		ENSP00000472415.1		M0R296

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

118866

Hom.:

AF XY:

0.0000782

AC XY:

AN XY:

63950

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000974

Gnomad SAS exome

AF:

0.000212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000219

Gnomad OTH exome

AF:

0.000813

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1358706

Hom.:

Cov.:

AF XY:

0.0000420

AC XY:

AN XY:

666876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000848

Gnomad4 SAS exome

AF:

0.0000794

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000263

Gnomad4 OTH exome

AF:

0.000264

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000543

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

May 10, 2023

The c.529C>T (p.R177W) alteration is located in exon 3 (coding exon 3) of the TMEM221 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the arginine (R) at amino acid position 177 to be replaced by a tryptophan (W). 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.036

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

L;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.9

D;.

REVEL

Benign

0.13

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.022

D;D

Vest4

0.29

MutPred

0.31

Loss of disorder (P = 0.006);.;

MVP

0.75

ClinPred

0.40

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.38

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