dbSNP rs369611318: TMEM44:p.Arg255Leu (chr3-194617118-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_001011655.3(TMEM44):c.764G>T(p.Arg255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,398,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R255H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMEM44
NM_001011655.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.651

Publications

0 publications found

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:

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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=0.16301507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM44	NM_001011655.3	MANE Select	c.764G>T	p.Arg255Leu	missense	Exon 6 of 10	NP_001011655.1	Q2T9K0-2
TMEM44	NM_001166305.2		c.905G>T	p.Arg302Leu	missense	Exon 7 of 11	NP_001159777.1	Q2T9K0-1
TMEM44	NM_138399.5		c.764G>T	p.Arg255Leu	missense	Exon 6 of 11	NP_612408.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM44	ENST00000347147.9	TSL:1 MANE Select	c.764G>T	p.Arg255Leu	missense	Exon 6 of 10	ENSP00000333355.6	Q2T9K0-2
TMEM44	ENST00000392432.6	TSL:1	c.905G>T	p.Arg302Leu	missense	Exon 7 of 11	ENSP00000376227.2	Q2T9K0-1
TMEM44	ENST00000473092.5	TSL:1	c.764G>T	p.Arg255Leu	missense	Exon 6 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

161320

AF XY:

0.0000117

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:

0.0000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1398038

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31786

American (AMR)

AF:

0.00

AC:

AN:

35538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24436

East Asian (EAS)

AF:

0.00

AC:

AN:

36378

South Asian (SAS)

AF:

0.0000128

AC:

AN:

78162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4286

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1080032

Other (OTH)

AF:

0.00

AC:

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000144

Hom.:

ExAC

AF:

0.00000862

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.83

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.65

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Benign

0.099

Sift

Benign

0.12

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.51

MVP

0.095

MPC

0.15

ClinPred

0.84

GERP RS

1.8

PromoterAI

0.068

Neutral

(source)

Varity_R

0.079

gMVP

0.56

Mutation Taster

=90/10

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over