Genetic Variant MROH6:p.Ala687Thr (chr8-143567340-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100878.2(MROH6):c.2059G>A(p.Ala687Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000475 in 1,219,852 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.99

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06068808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH6	NM_001100878.2	MANE Select	c.2059G>A	p.Ala687Thr	missense	Exon 14 of 14	NP_001094348.1	A6NGR9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH6	ENST00000398882.8	TSL:5 MANE Select	c.2059G>A	p.Ala687Thr	missense	Exon 14 of 14	ENSP00000381857.3	A6NGR9
MROH6	ENST00000533679.5	TSL:1	c.52G>A	p.Ala18Thr	missense	Exon 5 of 5	ENSP00000434244.1	E9PJR4
MROH6	ENST00000533210.5	TSL:1	n.1164G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000515

AC:

AN:

1068566

Hom.:

Cov.:

AF XY:

0.0000535

AC XY:

AN XY:

504604

show subpopulations

African (AFR)

AF:

0.0000893

AC:

AN:

22396

American (AMR)

AF:

0.00

AC:

AN:

7968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13668

East Asian (EAS)

AF:

0.00

AC:

AN:

25454

South Asian (SAS)

AF:

0.00

AC:

AN:

19970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21044

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

2844

European-Non Finnish (NFE)

AF:

0.0000559

AC:

AN:

912496

Other (OTH)

AF:

0.0000234

AC:

AN:

42726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151286

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73872

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67608

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.091

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.31

M_CAP

Benign

0.015

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.34

PhyloP100

-2.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.58

REVEL

Benign

0.013

Sift

Benign

0.55

Sift4G

Benign

0.31

Polyphen

0.41

Vest4

0.10

MVP

0.014

MPC

0.018

ClinPred

0.064

GERP RS

1.2

Varity_R

0.021

gMVP

0.055

Mutation Taster

=99/1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over