Variant rs6997753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000430863.5(MROH5):c.1304G>T(p.Arg435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MROH5
ENST00000430863.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.808

Variant links:

Genes affected

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

MROH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
MROH5	NR_102363.3 linkuse as main transcript	n.1270G>T	non_coding_transcript_exon_variant	10/28
MROH5	NR_102364.3 linkuse as main transcript	n.1411G>T	non_coding_transcript_exon_variant	11/27
MROH5	NR_160399.1 linkuse as main transcript	n.1384G>T	non_coding_transcript_exon_variant	11/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris
MROH5	ENST00000430863.5 linkuse as main transcript	c.1304G>T	p.Arg435Leu	missense_variant	11/30	1	P5
MROH5	ENST00000521053.5 linkuse as main transcript	c.*1070G>T		3_prime_UTR_variant, NMD_transcript_variant	10/28	5	A2
MROH5	ENST00000523857.5 linkuse as main transcript	c.*1211G>T		3_prime_UTR_variant, NMD_transcript_variant	11/27	2	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248060

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460928

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

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

May 26, 2024

The c.1304G>T (p.R435L) alteration is located in exon 11 (coding exon 11) of the MROH5 gene. This alteration results from a G to T substitution at nucleotide position 1304, causing the arginine (R) at amino acid position 435 to be replaced by a leucine (L). 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

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.66

MetaRNN

Uncertain

0.50

PrimateAI

Benign

0.32

Vest4

0.62

MVP

0.16

GERP RS

2.4

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