Variant 8-141434553-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000430863.5(MROH5):c.3854G>A(p.Arg1285His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,559,452 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

MROH5
ENST00000430863.5 missense, splice_region

Scores

Splicing: ADA: 0.00001497

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.52

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007772535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH5	NR_102363.3 linkuse as main transcript	n.3594G>A		splice_region_variant, non_coding_transcript_exon_variant	27/28
LOC107983985	XR_007061128.1 linkuse as main transcript	n.533C>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.3854G>A	p.Arg1285His	missense_variant, splice_region_variant	29/30	1	P5
	ENST00000606664.1 linkuse as main transcript	n.9C>T		non_coding_transcript_exon_variant	1/3	5
MROH5	ENST00000521053.5 linkuse as main transcript	c.*3397G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	27/28	5	A2
MROH5	ENST00000523857.5 linkuse as main transcript	c.*3385G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	26/27	2	A2

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000208

AC:

AN:

173142

Hom.:

AF XY:

0.000174

AC XY:

AN XY:

91802

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000264

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.000216

GnomAD4 exome

AF:

0.000303

AC:

427

AN:

1407234

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

205

AN XY:

694910

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.000295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000774

Gnomad4 FIN exome

AF:

0.000385

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.000359

GnomAD4 genome

AF:

0.000631

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000669

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00143

AC:

ESP6500EA

AF:

0.000476

AC:

ExAC

AF:

0.000185

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

Feb 17, 2023

The c.3854G>A (p.R1285H) alteration is located in exon 29 (coding exon 29) of the MROH5 gene. This alteration results from a G to A substitution at nucleotide position 3854, causing the arginine (R) at amino acid position 1285 to be replaced by a histidine (H). 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

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.85

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0078

PrimateAI

Benign

0.28

Vest4

0.073

MVP

0.061

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0080

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