Genetic Variant MROH6:p.Arg710Cys (chr8-143567271-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001100878.2(MROH6):c.2128C>T(p.Arg710Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,222,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R710H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.106846064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2128C>T	p.Arg710Cys	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.2128C>T	p.Arg710Cys	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000295

Gnomad OTH

AF:

0.000959

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1070752

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

505558

show subpopulations

African (AFR)

AF:

0.000889

AC:

AN:

22490

American (AMR)

AF:

0.000123

AC:

AN:

8110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13872

East Asian (EAS)

AF:

0.0000386

AC:

AN:

25888

South Asian (SAS)

AF:

0.00

AC:

AN:

19482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2856

European-Non Finnish (NFE)

AF:

0.00000547

AC:

AN:

914158

Other (OTH)

AF:

0.0000233

AC:

AN:

42892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000290

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.000916

AC:

AN:

41476

American (AMR)

AF:

0.000131

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67840

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000359

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2128C>T (p.R710C) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a C to T substitution at nucleotide position 2128, causing the arginine (R) at amino acid position 710 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.66

.;.;.;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;.

PhyloP100

2.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

N;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.040

B;.;.;.

Vest4

0.15

MutPred

0.20

Loss of methylation at R710 (P = 0.0115);.;.;.;

MVP

0.11

MPC

0.10

ClinPred

0.81

GERP RS

4.1

Varity_R

0.16

gMVP

0.11

Mutation Taster

=92/8

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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8-143567271-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over