Genetic Variant NM_001100878.2:c.2065C>T (chr8-143567334-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.2065C>T(p.Arg689Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,218,692 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

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=0.108410895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2065C>T	p.Arg689Cys	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.2065C>T	p.Arg689Cys	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000296

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.0000459

AC:

AN:

1067288

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

503948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22342

American (AMR)

AF:

0.00

AC:

AN:

7954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13624

East Asian (EAS)

AF:

0.00

AC:

AN:

25376

South Asian (SAS)

AF:

0.000152

AC:

AN:

19792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21010

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

2834

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

911722

Other (OTH)

AF:

0.0000469

AC:

AN:

42634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151404

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41350

American (AMR)

AF:

0.0000657

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67640

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2065C>T (p.R689C) 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 2065, causing the arginine (R) at amino acid position 689 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.1

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0035

T;.;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.47

.;.;.;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.20

N;.;.;.

PhyloP100

-1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.67

N;D;D;D

REVEL

Benign

0.11

Sift

Benign

0.16

T;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.99

D;.;.;.

Vest4

0.085

MutPred

0.21

Loss of MoRF binding (P = 0.0091);.;.;.;

MVP

0.076

MPC

0.019

ClinPred

0.27

GERP RS

0.30

Varity_R

0.058

gMVP

0.10

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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NM_001100878.2:c.2065C>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