Variant 8-144180454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032450.3(MROH1):c.493G>A(p.Val165Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,612,984 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MROH1
NM_032450.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

MROH1 (HGNC:26958): (maestro heat like repeat family member 1)

MROH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019586504).

BP6

Variant 8-144180454-G-A is Benign according to our data. Variant chr8-144180454-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3205138.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH1	NM_032450.3 link	c.493G>A	p.Val165Ile	missense_variant	7/44	ENST00000326134.10	NP_115826.3	Q8NDA8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH1	ENST00000326134.10 link	c.493G>A	p.Val165Ile	missense_variant	7/44	5	NM_032450.3	ENSP00000321737.5		Q8NDA8-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000165

AC:

AN:

248050

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000205

AC:

300

AN:

1460690

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

146

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000210

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000125

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.0000333

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.5

DANN

Benign

0.40

DEOGEN2

Benign

0.0038

.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.70

T;T;.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

N;.;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.15

N;N;N;N

REVEL

Benign

0.052

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0040

B;B;B;B

Vest4

0.18

MVP

0.043

MPC

0.17

ClinPred

0.0021

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.017

gMVP

0.20

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