Genetic Variant TMEM44:p.Gly356Arg (chr3-194604397-C-G) – 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.1066G>C(p.Gly356Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,389,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TMEM44
NM_001011655.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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:

LOC105374291 (HGNC:):

LOC105374291 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=0.10033944).

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.1066G>C	p.Gly356Arg	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
TMEM44	NM_001166305.2		c.1207G>C	p.Gly403Arg	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
TMEM44	NM_138399.5		c.1066G>C	p.Gly356Arg	missense	Exon 9 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.1066G>C	p.Gly356Arg	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
TMEM44	ENST00000392432.6	TSL:1	c.1207G>C	p.Gly403Arg	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
TMEM44	ENST00000473092.5	TSL:1	c.1066G>C	p.Gly356Arg	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1389128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31406

American (AMR)

AF:

0.00

AC:

AN:

34814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24722

East Asian (EAS)

AF:

0.00

AC:

AN:

35536

South Asian (SAS)

AF:

0.00

AC:

AN:

78620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00000373

AC:

AN:

1071866

Other (OTH)

AF:

0.00

AC:

AN:

57484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.73

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.1

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.014

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.59

Vest4

0.15

MutPred

0.19

Loss of loop (P = 0.0374)

MVP

0.040

MPC

0.20

ClinPred

0.71

GERP RS

2.0

Varity_R

0.080

gMVP

0.19

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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