8-141477837-C-T

Position:

• chr8-141477837-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000430863.5(MROH5):​c.1304G>A​(p.Arg435Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,613,172 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R435L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.037 (341 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (326 hom.)
• Consequence: MROH5 ENST00000430863.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808

Genes affected

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

MROH5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018429458).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH5	NR_102363.3	n.1270G>A		non_coding_transcript_exon_variant	10/28
MROH5	NR_102364.3	n.1411G>A		non_coding_transcript_exon_variant	11/27
MROH5	NR_160399.1	n.1384G>A		non_coding_transcript_exon_variant	11/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH5	ENST00000430863.5	c.1304G>A	p.Arg435Gln	missense_variant	11/30	1		ENSP00000431031.1

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5629 AN: 152128 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0102 AC: 2541 AN: 248060 Hom.: 124 AF XY: 0.00788 AC XY: 1063 AN XY: 134814

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.00787

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.000278

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.000703

Gnomad OTH exome AF: 0.00731

GnomAD4 exome AF: 0.00412 AC: 6019 AN: 1460926 Hom.: 326 Cov.: 33 AF XY: 0.00357 AC XY: 2595 AN XY: 726768

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.0000949

Gnomad4 NFE exome AF: 0.000469

Gnomad4 OTH exome AF: 0.00880

GnomAD4 genome AF: 0.0370 AC: 5636 AN: 152246 Hom.: 341 Cov.: 32 AF XY: 0.0365 AC XY: 2720 AN XY: 74444

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0148 Hom.: 84

Bravo AF: 0.0432

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.124 AC: 522

ESP6500EA AF: 0.000826 AC: 7

ExAC AF: 0.0124 AC: 1504

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0018	T
PrimateAI	Benign	0.28	T
Vest4		0.15
GERP RS		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs6997753; hg19: chr8-142487937; COSMIC: COSV101435955;