Genetic Variant NM_001011655.3:c.1063G>A (chr3-194604400-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001011655.3(TMEM44):c.1063G>A(p.Ala355Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,539,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A355A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TMEM44
NM_001011655.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.56

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018928051).

BP6

Variant 3-194604400-C-T is Benign according to our data. Variant chr3-194604400-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3458425.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1063G>A	p.Ala355Thr	missense	Exon 9 of 10	NP_001011655.1	Q2T9K0-2
TMEM44	NM_001166305.2		c.1204G>A	p.Ala402Thr	missense	Exon 10 of 11	NP_001159777.1	Q2T9K0-1
TMEM44	NM_138399.5		c.1063G>A	p.Ala355Thr	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.1063G>A	p.Ala355Thr	missense	Exon 9 of 10	ENSP00000333355.6	Q2T9K0-2
TMEM44	ENST00000392432.6	TSL:1	c.1204G>A	p.Ala402Thr	missense	Exon 10 of 11	ENSP00000376227.2	Q2T9K0-1
TMEM44	ENST00000473092.5	TSL:1	c.1063G>A	p.Ala355Thr	missense	Exon 9 of 11	ENSP00000418674.1	Q2T9K0-7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000464

AC:

AN:

150790

AF XY:

0.0000628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000269

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000516

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1387664

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

682508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31408

American (AMR)

AF:

0.00

AC:

AN:

34804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24662

East Asian (EAS)

AF:

0.0000845

AC:

AN:

35484

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.0000318

AC:

AN:

1070848

Other (OTH)

AF:

0.00

AC:

AN:

57420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

AF:

0.0000263

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41476

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00000919

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0020

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.00060

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.42

M_CAP

Benign

0.0048

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.77

PhyloP100

-2.6

PrimateAI

Benign

0.36

PROVEAN

Benign

0.80

REVEL

Benign

0.13

Sift

Benign

0.80

Sift4G

Benign

0.75

Polyphen

0.0060

Vest4

0.015

MVP

0.014

MPC

0.023

ClinPred

0.021

GERP RS

-9.8

Varity_R

0.021

gMVP

0.17

Mutation Taster

=99/1

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

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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