Genetic Variant MROH9:p.Met85Thr (chr1-170959563-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

Variant links:

Genes affected

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

MROH9 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH9	NM_001163629.2 link	c.254T>C	p.Met85Thr	missense_variant	Exon 5 of 22	ENST00000367759.9	NP_001157101.1	Q5TGP6-2
MROH9	NM_025063.4 link	c.254T>C	p.Met85Thr	missense_variant	Exon 5 of 15		NP_079339.2	Q5TGP6-1
MROH9	XM_011510005.3 link	c.254T>C	p.Met85Thr	missense_variant	Exon 5 of 21		XP_011508307.1
MROH9	XM_011510006.3 link	c.254T>C	p.Met85Thr	missense_variant	Exon 5 of 21		XP_011508308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH9	ENST00000367759.9 link	c.254T>C	p.Met85Thr	missense_variant	Exon 5 of 22	5	NM_001163629.2	ENSP00000356733.4		Q5TGP6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249204

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135216

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 SAS exome

AF:

0.0000328

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254T>C (p.M85T) alteration is located in exon 5 (coding exon 4) of the MROH9 gene. This alteration results from a T to C substitution at nucleotide position 254, causing the methionine (M) at amino acid position 85 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.84

DANN

Benign

0.79

DEOGEN2

Benign

0.0089

.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.027

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.63

.;P

Vest4

0.16

MutPred

0.34

Loss of catalytic residue at M85 (P = 0.0051);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over