dbSNP rs537602741: MROH6:p.Asp699Tyr (chr8-143567304-C-A) – 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.2095G>T(p.Asp699Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,221,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.743

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=0.05454147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2 link	c.2095G>T	p.Asp699Tyr	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.2095G>T	p.Asp699Tyr	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3		A6NGR9

Frequencies

GnomAD3 genomes

AF:

0.000475

AC:

AN:

151690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

Gnomad OTH

AF:

0.000959

GnomAD4 exome

AF:

0.0000795

AC:

AN:

1069324

Hom.:

Cov.:

AF XY:

0.0000733

AC XY:

AN XY:

504858

show subpopulations

African (AFR)

AF:

0.00169

AC:

AN:

22444

American (AMR)

AF:

0.00

AC:

AN:

8042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13772

East Asian (EAS)

AF:

0.00

AC:

AN:

25678

South Asian (SAS)

AF:

0.00

AC:

AN:

19538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2846

European-Non Finnish (NFE)

AF:

0.0000460

AC:

AN:

913252

Other (OTH)

AF:

0.000117

AC:

AN:

42762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000474

AC:

AN:

151798

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41446

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67836

Other (OTH)

AF:

0.000949

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:

0.000495

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 16, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2095G>T (p.D699Y) alteration is located in exon 14 (coding exon 14) of the MROH6 gene. This alteration results from a G to T substitution at nucleotide position 2095, causing the aspartic acid (D) at amino acid position 699 to be replaced by a tyrosine (Y). 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

0.22

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0075

T;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.53

.;.;.;T

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;.

PhyloP100

0.74

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;D;D;D

REVEL

Benign

0.084

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.95

P;.;.;.

Vest4

0.26

MVP

0.12

MPC

0.13

ClinPred

0.68

GERP RS

3.2

Varity_R

0.12

gMVP

0.38

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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rs537602741

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