Genetic Variant MROH6:p.Arg673His (chr8-143567381-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100878.2(MROH6):c.2018G>A(p.Arg673His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000097 in 1,237,272 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.861

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061519235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2018G>A	p.Arg673His	missense_variant	Exon 14 of 14	ENST00000398882.8	NP_001094348.1	A6NGR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH6	ENST00000398882.8 link	c.2018G>A	p.Arg673His	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00

AC:

AN:

1304

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000921

AC:

AN:

1086118

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

514006

show subpopulations

African (AFR)

AF:

0.0000438

AC:

AN:

22812

American (AMR)

AF:

0.000120

AC:

AN:

8304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14292

East Asian (EAS)

AF:

0.00

AC:

AN:

26360

South Asian (SAS)

AF:

0.00

AC:

AN:

22546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2926

European-Non Finnish (NFE)

AF:

0.00000758

AC:

AN:

923238

Other (OTH)

AF:

0.0000228

AC:

AN:

43838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73798

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41264

American (AMR)

AF:

0.000132

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67560

Other (OTH)

AF:

0.00

AC:

AN:

2072

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:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2018G>A (p.R673H) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a G to A substitution at nucleotide position 2018, causing the arginine (R) at amino acid position 673 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.3

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0010

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.31

.;.;.;T;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.062

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.28

N;.;.;.;.

PhyloP100

-0.86

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.73

N;N;N;N;D

REVEL

Benign

0.011

Sift

Benign

0.27

T;T;T;T;.

Sift4G

Uncertain

0.038

D;T;T;T;.

Polyphen

0.062

B;.;.;.;.

Vest4

0.087

MutPred

0.34

Loss of methylation at R673 (P = 0.0029);.;.;.;.;

MVP

0.014

MPC

0.018

ClinPred

0.037

GERP RS

-1.8

Varity_R

0.027

gMVP

0.10

Mutation Taster

=93/7

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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8-143567381-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over