Genetic Variant MROH6:p.Arg673Leu (chr8-143567381-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100878.2(MROH6):c.2018G>T(p.Arg673Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R673H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071050346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2018G>T	p.Arg673Leu	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>T	p.Arg673Leu	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1086118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

514006

African (AFR)

AF:

0.00

AC:

AN:

22812

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

923238

Other (OTH)

AF:

0.00

AC:

AN:

43838

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73798

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41264

American (AMR)

AF:

0.00

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:

0.0000148

AC:

AN:

67560

Other (OTH)

AF:

0.00

AC:

AN:

2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.2

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0086

T;.;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.27

.;.;.;T;.

M_CAP

Benign

0.036

MetaRNN

Benign

0.071

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.97

L;.;.;.;.

PhyloP100

-0.86

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.9

N;D;D;D;D

REVEL

Benign

0.016

Sift

Benign

0.18

T;T;T;T;.

Sift4G

Uncertain

0.046

D;T;T;T;.

Polyphen

0.0010

B;.;.;.;.

Vest4

0.12

MutPred

0.33

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

MVP

0.030

MPC

0.018

ClinPred

0.049

GERP RS

-1.8

Varity_R

0.060

gMVP

0.16

Mutation Taster

=97/3

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over