Genetic Variant TMEM81:p.Arg77Gln (chr1-205084091-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203376.2(TMEM81):c.230G>A(p.Arg77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 1,613,970 control chromosomes in the GnomAD database, including 602,838 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49799 hom., cov: 31)

Exomes 𝑓: 0.87 ( 553039 hom. )

Consequence

TMEM81
NM_203376.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

40 publications found

Variant links:

Genes affected

TMEM81 (HGNC:32349): (transmembrane protein 81) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM81 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.531576E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203376.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM81	NM_203376.2	MANE Select	c.230G>A	p.Arg77Gln	missense	Exon 1 of 1	NP_976310.1	Q6P7N7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM81	ENST00000367167.4	TSL:6 MANE Select	c.230G>A	p.Arg77Gln	missense	Exon 1 of 1	ENSP00000356135.3	Q6P7N7

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121526

AN:

151978

Hom.:

49783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.929

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.970

Gnomad SAS

AF:

0.912

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.841

GnomAD2 exomes

AF:

0.871

AC:

219028

AN:

251438

AF XY:

0.874

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.924

Gnomad ASJ exome

AF:

0.864

Gnomad EAS exome

AF:

0.973

Gnomad FIN exome

AF:

0.893

Gnomad NFE exome

AF:

0.865

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.868

AC:

1269115

AN:

1461874

Hom.:

553039

Cov.:

AF XY:

0.869

AC XY:

632194

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.575

AC:

19265

AN:

33480

American (AMR)

AF:

0.921

AC:

41181

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

22397

AN:

26136

East Asian (EAS)

AF:

0.967

AC:

38401

AN:

39700

South Asian (SAS)

AF:

0.903

AC:

77916

AN:

86254

European-Finnish (FIN)

AF:

0.891

AC:

47604

AN:

53420

Middle Eastern (MID)

AF:

0.810

AC:

4671

AN:

5768

European-Non Finnish (NFE)

AF:

0.868

AC:

965674

AN:

1111996

Other (OTH)

AF:

0.861

AC:

52006

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10005

20010

30016

40021

50026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21258

42516

63774

85032

106290

<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:

0.799

AC:

121581

AN:

152096

Hom.:

49799

Cov.:

AF XY:

0.803

AC XY:

59726

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.597

AC:

24744

AN:

41432

American (AMR)

AF:

0.880

AC:

13459

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2993

AN:

3470

East Asian (EAS)

AF:

0.970

AC:

5011

AN:

5164

South Asian (SAS)

AF:

0.912

AC:

4398

AN:

4820

European-Finnish (FIN)

AF:

0.889

AC:

9427

AN:

10606

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58666

AN:

67996

Other (OTH)

AF:

0.843

AC:

1782

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1150

2301

3451

4602

5752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.844

Hom.:

235287

Bravo

AF:

0.793

TwinsUK

AF:

0.864

AC:

3204

ALSPAC

AF:

0.874

AC:

3369

ESP6500AA

AF:

0.603

AC:

2657

ESP6500EA

AF:

0.863

AC:

7424

ExAC

AF:

0.864

AC:

104938

Asia WGS

AF:

0.928

AC:

3226

AN:

3478

EpiCase

AF:

0.862

EpiControl

AF:

0.861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.20

MetaRNN

Benign

6.5e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.9

PhyloP100

0.25

PrimateAI

Benign

0.34

PROVEAN

Benign

0.31

REVEL

Benign

0.097

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.029

MPC

0.078

ClinPred

0.0081

GERP RS

5.5

PromoterAI

0.033

Neutral

(source)

Varity_R

0.025

gMVP

0.50

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over