Genetic Variant NM_001163629.2:c.254T>C (chr1-170959563-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001163629.2(MROH9):c.254T>C(p.Met85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MROH9
NM_001163629.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.463

Publications

0 publications found

Variant links:

Genes affected

MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

MROH9 links:

FMO1-AS1 (HGNC:40240):

FMO1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09146619).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163629.2. 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
	MROH9	NM_001163629.2	MANE Select	c.254T>C	p.Met85Thr	missense	Exon 5 of 22	NP_001157101.1	Q5TGP6-2
	MROH9	NM_025063.4		c.254T>C	p.Met85Thr	missense	Exon 5 of 15	NP_079339.2	Q5TGP6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH9	ENST00000367759.9	TSL:5 MANE Select	c.254T>C	p.Met85Thr	missense	Exon 5 of 22	ENSP00000356733.4	Q5TGP6-2
MROH9	ENST00000367758.7	TSL:1	c.254T>C	p.Met85Thr	missense	Exon 5 of 15	ENSP00000356732.3	Q5TGP6-1
MROH9	ENST00000864982.1		c.254T>C	p.Met85Thr	missense	Exon 5 of 21	ENSP00000535041.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249204

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461498

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111834

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

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

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

Cov.:

ExAC

AF:

0.00000828

AC:

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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.84

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.32

M_CAP

Benign

0.0064

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

PhyloP100

-0.46

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

REVEL

Benign

0.027

Sift

Benign

0.12

Sift4G

Uncertain

0.0090

Polyphen

0.63

Vest4

0.16

MutPred

0.34

Loss of catalytic residue at M85 (P = 0.0051)

MVP

0.22

MPC

0.088

ClinPred

0.11

GERP RS

0.20

Varity_R

0.078

gMVP

0.076

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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