Genetic Variant MROH6:p.Val707Ile (chr8-143567280-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001100878.2(MROH6):c.2119G>A(p.Val707Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,222,560 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.141

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0398463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2119G>A	p.Val707Ile	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.2119G>A	p.Val707Ile	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1070644

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

505480

show subpopulations

African (AFR)

AF:

0.000178

AC:

AN:

22494

American (AMR)

AF:

0.00

AC:

AN:

8106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13866

East Asian (EAS)

AF:

0.00

AC:

AN:

25888

South Asian (SAS)

AF:

0.00

AC:

AN:

19490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2854

European-Non Finnish (NFE)

AF:

0.0000263

AC:

AN:

914060

Other (OTH)

AF:

0.0000233

AC:

AN:

42874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000138

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41490

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67852

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000117

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 26, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2119G>A (p.V707I) 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 2119, causing the valine (V) at amino acid position 707 to be replaced by an isoleucine (I). 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

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.0

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0017

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.33

.;.;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;.;.;.

PhyloP100

-0.14

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.030

N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.019

B;.;.;.

Vest4

0.033

MutPred

0.087

Loss of methylation at R710 (P = 0.1009);.;.;.;

MVP

0.014

MPC

0.017

ClinPred

0.059

GERP RS

3.1

Varity_R

0.026

gMVP

0.022

Mutation Taster

=98/2

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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8-143567280-C-T

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