Variant 3-194611012-A-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.921T>A(p.Asp307Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,540 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: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

TMEM44
NM_001011655.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.04

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=0.19483694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM44	NM_001011655.3 link	c.921T>A	p.Asp307Glu	missense_variant	8/10	ENST00000347147.9	NP_001011655.1	Q2T9K0-2
TMEM44	NM_001166305.2 link	c.1062T>A	p.Asp354Glu	missense_variant	9/11		NP_001159777.1	Q2T9K0-1
TMEM44	NM_138399.5 link	c.921T>A	p.Asp307Glu	missense_variant	8/11		NP_612408.3	Q2T9K0-7
TMEM44	NM_001166306.2 link	c.921T>A	p.Asp307Glu	missense_variant	8/10		NP_001159778.1	Q2T9K0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM44	ENST00000347147.9 link	c.921T>A	p.Asp307Glu	missense_variant	8/10	1	NM_001011655.3	ENSP00000333355.6		Q2T9K0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250944

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135600

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 SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461540

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00144

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

Mar 19, 2024

The c.1062T>A (p.D354E) alteration is located in exon 9 (coding exon 9) of the TMEM44 gene. This alteration results from a T to A substitution at nucleotide position 1062, causing the aspartic acid (D) at amino acid position 354 to be replaced by a glutamic acid (E). 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

0.42

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

DANN

Benign

0.96

DEOGEN2

Benign

0.0078

T;T;.;.;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.62

T;T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

L;.;.;.;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N;N;N;N;N;D

REVEL

Benign

0.18

Sift

Benign

0.12

T;D;T;T;T;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

D;.;B;D;.;.;D

Vest4

0.17

MutPred

0.56

Loss of loop (P = 0.0153);.;.;.;.;.;.;

MVP

0.061

MPC

0.16

ClinPred

0.48

GERP RS

-10

Varity_R

0.064

gMVP

0.094

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