Genetic Variant MROH9:p.Asn101Ser (chr1-170961903-A-G) – 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_001163629.2(MROH9):c.302A>G(p.Asn101Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,492,130 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MROH9
NM_001163629.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.03

Publications

1 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:

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=0.061706036).

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.302A>G	p.Asn101Ser	missense	Exon 6 of 22	NP_001157101.1	Q5TGP6-2
	MROH9	NM_025063.4		c.302A>G	p.Asn101Ser	missense	Exon 6 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.302A>G	p.Asn101Ser	missense	Exon 6 of 22	ENSP00000356733.4	Q5TGP6-2
MROH9	ENST00000367758.7	TSL:1	c.302A>G	p.Asn101Ser	missense	Exon 6 of 15	ENSP00000356732.3	Q5TGP6-1
MROH9	ENST00000864982.1		c.302A>G	p.Asn101Ser	missense	Exon 6 of 21	ENSP00000535041.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000266

AC:

AN:

187998

AF XY:

0.0000193

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:

0.0000436

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1339950

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

668198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28108

American (AMR)

AF:

0.00

AC:

AN:

30568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24092

East Asian (EAS)

AF:

0.00

AC:

AN:

34906

South Asian (SAS)

AF:

0.0000275

AC:

AN:

72680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52238

Middle Eastern (MID)

AF:

0.000375

AC:

AN:

5332

European-Non Finnish (NFE)

AF:

0.0000183

AC:

AN:

1036356

Other (OTH)

AF:

0.00

AC:

AN:

55670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000166

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

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

0.072

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0070

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.48

M_CAP

Benign

0.010

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

PhyloP100

-2.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

REVEL

Benign

0.024

Sift

Benign

0.54

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.090

MutPred

0.41

Loss of catalytic residue at N101 (P = 0.0365)

MVP

0.21

MPC

0.048

ClinPred

0.021

GERP RS

-11

Varity_R

0.036

gMVP

0.037

Mutation Taster

=100/0

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