Variant chr8-141434058-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000430863.5(MROH5):c.3857C>A(p.Thr1286Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 145,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MROH5
ENST00000430863.5 missense, splice_region

Scores

Splicing: ADA: 0.00001171

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

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

MROH5 links:

LOC107983985 (HGNC:):

LOC107983985 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=0.13916963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
MROH5	NR_102363.3 linkuse as main transcript	n.3597C>A	splice_region_variant, non_coding_transcript_exon_variant	28/28
LOC107983985	XR_007061128.1 linkuse as main transcript	n.38G>T	non_coding_transcript_exon_variant	1/3
MROH5	NR_102364.3 linkuse as main transcript	n.3588C>A	splice_region_variant, non_coding_transcript_exon_variant	27/27
MROH5	NR_160399.1 linkuse as main transcript	n.3937C>A	splice_region_variant, non_coding_transcript_exon_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris
MROH5	ENST00000430863.5 linkuse as main transcript	c.3857C>A	p.Thr1286Asn	missense_variant, splice_region_variant	30/30	1	P5
MROH5	ENST00000521053.5 linkuse as main transcript	c.*3400C>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	28/28	5	A2
MROH5	ENST00000523857.5 linkuse as main transcript	c.*3388C>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	27/27	2	A2

Frequencies

GnomAD3 genomes

AF:

0.00000685

AC:

AN:

145916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237196

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129018

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000484

AC:

AN:

1445214

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

718452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000544

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000685

AC:

AN:

145916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000113

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

Aug 16, 2021

The c.3857C>A (p.T1286N) alteration is located in exon 30 (coding exon 30) of the MROH5 gene. This alteration results from a C to A substitution at nucleotide position 3857, causing the threonine (T) at amino acid position 1286 to be replaced by an asparagine (N). 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

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.69

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.43

MetaRNN

Benign

0.14

PrimateAI

Uncertain

0.51

Vest4

0.21

MVP

0.048

GERP RS

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

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