Variant 8-141435203-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000430863.5(MROH5):c.3602G>A(p.Arg1201Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,612,674 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

MROH5
ENST00000430863.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

MROH5 (HGNC:42976): (maestro heat like repeat family member 5 (gene/pseudogene))

MROH5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013793081).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH5	NR_102363.3 linkuse as main transcript	n.3342G>A		non_coding_transcript_exon_variant	25/28
LOC107983985	XR_007061128.1 linkuse as main transcript	n.1183C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris
MROH5	ENST00000430863.5 linkuse as main transcript	c.3602G>A	p.Arg1201Gln	missense_variant	27/30	1	P5
	ENST00000606664.1 linkuse as main transcript	n.659C>T		non_coding_transcript_exon_variant	1/3	5
MROH5	ENST00000521053.5 linkuse as main transcript	c.*3145G>A		3_prime_UTR_variant, NMD_transcript_variant	25/28	5	A2
MROH5	ENST00000523857.5 linkuse as main transcript	c.*3236G>A		3_prime_UTR_variant, NMD_transcript_variant	25/27	2	A2

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000455

AC:

112

AN:

246372

Hom.:

AF XY:

0.000470

AC XY:

AN XY:

134164

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000465

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.000280

Gnomad NFE exome

AF:

0.000623

Gnomad OTH exome

AF:

0.000834

GnomAD4 exome

AF:

0.000550

AC:

803

AN:

1460346

Hom.:

Cov.:

AF XY:

0.000546

AC XY:

397

AN XY:

726472

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000452

Gnomad4 FIN exome

AF:

0.000286

Gnomad4 NFE exome

AF:

0.000630

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000551

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000591

Hom.:

Bravo

AF:

0.000389

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000707

AC:

ExAC

AF:

0.000421

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.3602G>A (p.R1201Q) alteration is located in exon 27 (coding exon 27) of the MROH5 gene. This alteration results from a G to A substitution at nucleotide position 3602, causing the arginine (R) at amino acid position 1201 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.1

DANN

Benign

0.83

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.45

MetaRNN

Benign

0.014

PrimateAI

Benign

0.36

Vest4

0.13

MVP

0.085

GERP RS

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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