Genetic Variant MROH9:p.Gln236Lys (chr1-170983511-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001163629.2(MROH9):c.706C>A(p.Gln236Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00852 in 1,611,656 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 68 hom. )

Consequence

MROH9
NM_001163629.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

MROH9 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004406631).

BP6

Variant 1-170983511-C-A is Benign according to our data. Variant chr1-170983511-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH9	NM_001163629.2 link	c.706C>A	p.Gln236Lys	missense_variant	Exon 9 of 22	ENST00000367759.9	NP_001157101.1	Q5TGP6-2
MROH9	NM_025063.4 link	c.706C>A	p.Gln236Lys	missense_variant	Exon 9 of 15		NP_079339.2	Q5TGP6-1
MROH9	XM_011510005.3 link	c.706C>A	p.Gln236Lys	missense_variant	Exon 9 of 21		XP_011508307.1
MROH9	XM_011510006.3 link	c.706C>A	p.Gln236Lys	missense_variant	Exon 9 of 21		XP_011508308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH9	ENST00000367759.9 link	c.706C>A	p.Gln236Lys	missense_variant	Exon 9 of 22	5	NM_001163629.2	ENSP00000356733.4		Q5TGP6-2

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

974

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00972

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00626

AC:

1556

AN:

248634

Hom.:

AF XY:

0.00642

AC XY:

866

AN XY:

134934

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00920

Gnomad OTH exome

AF:

0.00647

GnomAD4 exome

AF:

0.00874

AC:

12755

AN:

1459390

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

6312

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.00419

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.00640

AC:

974

AN:

152266

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

484

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.00972

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00570

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00221

AC:

ESP6500EA

AF:

0.00871

AC:

ExAC

AF:

0.00619

AC:

748

Asia WGS

AF:

0.00116

AC:

AN:

3474

EpiCase

AF:

0.00830

EpiControl

AF:

0.00867

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MROH9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.52

DANN

Benign

0.30

DEOGEN2

Benign

0.0059

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.015

Sift

Benign

0.92

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0080

.;B

Vest4

0.061

MVP

0.11

MPC

0.068

ClinPred

0.0013

GERP RS

-5.2

Varity_R

0.056

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over