Genetic Variant MROH6:p.Arg710His (chr8-143567270-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001100878.2(MROH6):c.2129G>A(p.Arg710His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,222,190 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R710C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.154

Publications

1 publications found

Variant links:

Genes affected

MROH6 (HGNC:27814): (maestro heat like repeat family member 6)

MROH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018553495).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100878.2. 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
	MROH6	NM_001100878.2	MANE Select	c.2129G>A	p.Arg710His	missense	Exon 14 of 14	NP_001094348.1	A6NGR9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH6	ENST00000398882.8	TSL:5 MANE Select	c.2129G>A	p.Arg710His	missense	Exon 14 of 14	ENSP00000381857.3	A6NGR9
MROH6	ENST00000533679.5	TSL:1	c.122G>A	p.Arg41His	missense	Exon 5 of 5	ENSP00000434244.1	E9PJR4
MROH6	ENST00000533210.5	TSL:1	n.1234G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.000310

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000205

AC:

219

AN:

1070320

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

114

AN XY:

505334

show subpopulations

African (AFR)

AF:

0.000223

AC:

AN:

22470

American (AMR)

AF:

0.000741

AC:

AN:

8100

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

13844

East Asian (EAS)

AF:

0.00

AC:

AN:

25874

South Asian (SAS)

AF:

0.000616

AC:

AN:

19478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21004

Middle Eastern (MID)

AF:

0.00561

AC:

AN:

2854

European-Non Finnish (NFE)

AF:

0.000165

AC:

151

AN:

913842

Other (OTH)

AF:

0.000490

AC:

AN:

42854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000336

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41474

American (AMR)

AF:

0.000916

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00145

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000310

AC:

AN:

67838

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000351

ExAC

AF:

0.00251

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.54

M_CAP

Benign

0.049

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

PhyloP100

0.15

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.0

REVEL

Benign

0.033

Sift

Benign

0.035

Sift4G

Pathogenic

0.0

Polyphen

0.010

Vest4

0.097

MVP

0.014

MPC

0.021

ClinPred

0.44

GERP RS

2.0

Varity_R

0.036

gMVP

0.095

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over