20-37178722-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152503.8(MROH8):c.257+501G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,010 control chromosomes in the GnomAD database, including 12,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12004 hom., cov: 30)
  • Exomes 𝑓: 0.20 (10 hom.)
• Consequence: MROH8 NM_152503.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.555

Genes affected

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

RPN2 (HGNC:10382): (ribophorin II) This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein is similar in sequence to the yeast oligosaccharyl transferase subunit SWP1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-37178722-C-A is Benign according to our data. Variant chr20-37178722-C-A is described in ClinVar as [Benign]. Clinvar id is 1238363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH8	NM_152503.8	c.257+501G>T		intron_variant		ENST00000710289.2
MROH8	NM_213631.3	c.257+501G>T		intron_variant
MROH8	NM_213632.3	c.257+501G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH8	ENST00000343811.10	c.257+501G>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57544 AN: 151546 Hom.: 11989 Cov.: 30

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.199 AC: 69 AN: 346 Hom.: 10 Cov.: 0 AF XY: 0.180 AC XY: 51 AN XY: 284

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.380 AC: 57585 AN: 151664 Hom.: 12004 Cov.: 30 AF XY: 0.372 AC XY: 27582 AN XY: 74122

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.00986

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.382

Alfa AF: 0.221 Hom.: 448

Bravo AF: 0.384

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.9
Dann	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2880502; hg19: chr20-35807125;