Genetic Variant MROH8:p.Gln916Arg (chr20-37112391-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000343811.10(MROH8):c.2747A>G(p.Gln916Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,355,222 control chromosomes in the GnomAD database, including 160,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 0.42 ( 14492 hom., cov: 32)

Exomes 𝑓: 0.49 ( 146022 hom. )

Consequence

MROH8
ENST00000343811.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.196

Publications

25 publications found

Variant links:

Genes affected

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

MROH8 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=1.3868186E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8 link	c.2747A>G	p.Gln916Arg	missense_variant	Exon 21 of 25		NP_689716.4	Q9H579Q0P682

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10 link	c.2747A>G	p.Gln916Arg	missense_variant	Exon 21 of 25	1		ENSP00000513568.1		A0A8V8TLY2
MROH8	ENST00000422138.2 link	c.2489A>G	p.Gln830Arg	missense_variant	Exon 19 of 23	3		ENSP00000400468.2		Q5JYQ9

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63577

AN:

151896

Hom.:

14486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.472

AC:

112933

AN:

239136

AF XY:

0.481

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.519

Gnomad EAS exome

AF:

0.460

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.489

AC:

587827

AN:

1203208

Hom.:

146022

Cov.:

AF XY:

0.492

AC XY:

293500

AN XY:

596160

show subpopulations

African (AFR)

AF:

0.215

AC:

5552

AN:

25850

American (AMR)

AF:

0.493

AC:

17360

AN:

35236

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

8634

AN:

16528

East Asian (EAS)

AF:

0.469

AC:

7455

AN:

15906

South Asian (SAS)

AF:

0.576

AC:

46684

AN:

80984

European-Finnish (FIN)

AF:

0.428

AC:

13858

AN:

32414

Middle Eastern (MID)

AF:

0.454

AC:

2011

AN:

4428

European-Non Finnish (NFE)

AF:

0.491

AC:

465360

AN:

948484

Other (OTH)

AF:

0.482

AC:

20913

AN:

43378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14545

29090

43634

58179

72724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15646

31292

46938

62584

78230

<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:

0.418

AC:

63602

AN:

152014

Hom.:

14492

Cov.:

AF XY:

0.421

AC XY:

31286

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.227

AC:

9410

AN:

41512

American (AMR)

AF:

0.512

AC:

7816

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1809

AN:

3470

East Asian (EAS)

AF:

0.485

AC:

2511

AN:

5172

South Asian (SAS)

AF:

0.586

AC:

2820

AN:

4816

European-Finnish (FIN)

AF:

0.419

AC:

4424

AN:

10556

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33313

AN:

67920

Other (OTH)

AF:

0.429

AC:

905

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.471

Hom.:

81852

Bravo

AF:

0.413

TwinsUK

AF:

0.489

AC:

1812

ALSPAC

AF:

0.505

AC:

1947

ESP6500AA

AF:

0.239

AC:

906

ESP6500EA

AF:

0.480

AC:

3955

ExAC

AF:

0.477

AC:

57581

Asia WGS

AF:

0.522

AC:

1812

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.5

(source)

DANN

Benign

0.40

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.29

MetaRNN

Benign

0.000014

MetaSVM

Benign

-0.96

PhyloP100

-0.20

PrimateAI

Benign

0.22

PROVEAN

Benign

0.56

REVEL

Benign

0.051

Sift

Benign

0.91

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.034

ClinPred

0.0019

GERP RS

-3.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over