Genetic Variant NM_001100878.2:c.2092G>A (chr8-143567307-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.2092G>A(p.Ala698Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000983 in 1,220,938 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MROH6
NM_001100878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.416

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=0.049613208).

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.2092G>A	p.Ala698Thr	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.2092G>A	p.Ala698Thr	missense	Exon 14 of 14	ENSP00000381857.3	A6NGR9
MROH6	ENST00000533679.5	TSL:1	c.85G>A	p.Ala29Thr	missense	Exon 5 of 5	ENSP00000434244.1	E9PJR4
MROH6	ENST00000533210.5	TSL:1	n.1197G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1069246

Hom.:

Cov.:

AF XY:

0.00000990

AC XY:

AN XY:

504812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22440

American (AMR)

AF:

0.00

AC:

AN:

8034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13768

East Asian (EAS)

AF:

0.000117

AC:

AN:

25644

South Asian (SAS)

AF:

0.00

AC:

AN:

19532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2842

European-Non Finnish (NFE)

AF:

0.00000767

AC:

AN:

913240

Other (OTH)

AF:

0.0000234

AC:

AN:

42754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.00000659

AC:

AN:

151692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41340

American (AMR)

AF:

0.0000656

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.089

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.4

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0070

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.36

M_CAP

Benign

0.036

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

PhyloP100

-0.42

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.35

REVEL

Benign

0.036

Sift

Benign

0.11

Sift4G

Uncertain

0.036

Polyphen

0.048

Vest4

0.035

MutPred

0.048

Gain of phosphorylation at A698 (P = 0.0129)

MVP

0.014

MPC

0.017

ClinPred

0.071

GERP RS

0.47

Varity_R

0.029

gMVP

0.059

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over