Variant chr3-194617118-C-T 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_001011655.3(TMEM44):c.764G>A(p.Arg255His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,550,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

TMEM44
NM_001011655.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.651

Variant links:

Genes affected

TMEM44 (HGNC:25120): (transmembrane protein 44) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM44 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=0.07677546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM44	NM_001011655.3 link	c.764G>A	p.Arg255His	missense_variant	6/10	ENST00000347147.9	NP_001011655.1	Q2T9K0-2
TMEM44	NM_001166305.2 link	c.905G>A	p.Arg302His	missense_variant	7/11		NP_001159777.1	Q2T9K0-1
TMEM44	NM_138399.5 link	c.764G>A	p.Arg255His	missense_variant	6/11		NP_612408.3	Q2T9K0-7
TMEM44	NM_001166306.2 link	c.764G>A	p.Arg255His	missense_variant	6/10		NP_001159778.1	Q2T9K0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9 link	c.764G>A	p.Arg255His	missense_variant	6/10	1	NM_001011655.3	ENSP00000333355.6		Q2T9K0-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000682

AC:

AN:

161320

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

85456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000916

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000230

AC:

322

AN:

1398036

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

159

AN XY:

689974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000563

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000275

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000105

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000345

AC:

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

Jan 20, 2023

The c.905G>A (p.R302H) alteration is located in exon 7 (coding exon 7) of the TMEM44 gene. This alteration results from a G to A substitution at nucleotide position 905, causing the arginine (R) at amino acid position 302 to be replaced by a histidine (H). 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

0.41

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0029

T;T;.;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.75

T;T;T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.077

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.83

N;N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

0.58

P;.;B;B;.

Vest4

0.29

MVP

0.14

MPC

0.18

ClinPred

0.069

GERP RS

1.8

Varity_R

0.038

gMVP

0.37

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