Variant rs75269200 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039464.4(MROH7):c.1988A>G(p.Lys663Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,080 control chromosomes in the GnomAD database, including 703 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.035 ( 219 hom., cov: 32)

Exomes 𝑓: 0.011 ( 484 hom. )

Consequence

MROH7
NM_001039464.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

MROH7 (HGNC:24802): (maestro heat like repeat family member 7) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MROH7 links:

MROH7-TTC4 (HGNC:49180): (MROH7-TTC4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MROH7 (maestro heat-like repeat family member 7) and TTC4 (tetratricopeptide repeat domain 4) genes. Alternative splicing results in multiple transcript variants, which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to produce protein products. [provided by RefSeq, Aug 2013]

MROH7-TTC4 links:

MROH7 (HGNC:):

MROH7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025929213).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH7	NM_001039464.4 linkuse as main transcript	c.1988A>G	p.Lys663Arg	missense_variant	11/24	ENST00000421030.7	NP_001034553.3	Q68CQ1-7B7Z7S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7 linkuse as main transcript	c.1988A>G	p.Lys663Arg	missense_variant	11/24	2	NM_001039464.4	ENSP00000396622.2		Q68CQ1-7
MROH7-TTC4	ENST00000414150.6 linkuse as main transcript	n.1988A>G		non_coding_transcript_exon_variant	11/33	2		ENSP00000410192.2		A0A0A0MT08

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5262

AN:

152138

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.0577

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0233

AC:

5823

AN:

249570

Hom.:

188

AF XY:

0.0227

AC XY:

3073

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.0883

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.0693

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.00282

Gnomad OTH exome

AF:

0.0165

GnomAD4 exome

AF:

0.0105

AC:

15414

AN:

1461824

Hom.:

484

Cov.:

AF XY:

0.0112

AC XY:

8142

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0908

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0821

Gnomad4 SAS exome

AF:

0.0440

Gnomad4 FIN exome

AF:

0.0369

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0348

AC:

5293

AN:

152256

Hom.:

219

Cov.:

AF XY:

0.0369

AC XY:

2747

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0665

Gnomad4 SAS

AF:

0.0578

Gnomad4 FIN

AF:

0.0397

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.0339

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0767

AC:

302

ESP6500EA

AF:

0.00290

AC:

ExAC

AF:

0.0250

AC:

3019

Asia WGS

AF:

0.0870

AC:

300

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0042

.;T;.;.

Eigen

Benign

-0.0099

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.60

T;T;T;T

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.3

.;L;.;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.87

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.93

P;B;.;.

Vest4

0.14

MPC

0.29

ClinPred

0.025

GERP RS

3.9

Varity_R

0.074

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over