20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_152503.8(MROH8):c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTATAAG(p.Asn31LysfsTer10) variant causes a splice donor, stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,507,500 control chromosomes in the GnomAD database, including 483,994 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (52352 hom., cov: 0)
  • Exomes 𝑓: 0.80 (431642 hom.)
• Consequence: MROH8 NM_152503.8 splice_donor, stop_gained, frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659

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 -8 ACMG points.

• PM4: Stoplost variant in NM_152503.8 Downstream stopcodon found after 781 codons.
• BP6: Variant 20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT is described in ClinVar as [Likely_benign]. Clinvar id is 1115482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH8	NM_152503.8	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTATAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		ENST00000710289.2
RPN2	NM_002951.5	c.13+21_13+22insATAGACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		ENST00000237530.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTATAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		1		P2
RPN2	ENST00000237530.11	c.13+21_13+22insATAGACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		1	NM_002951.5	P1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125068 AN: 151842 Hom.: 52316 Cov.: 0

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.796 AC: 1078807 AN: 1355542 Hom.: 431642 Cov.: 83 AF XY: 0.794 AC XY: 526884 AN XY: 663612

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.724

Gnomad4 ASJ exome AF: 0.842

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.801

GnomAD4 genome AF: 0.824 AC: 125160 AN: 151958 Hom.: 52352 Cov.: 0 AF XY: 0.816 AC XY: 60633 AN XY: 74266

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.837

Alfa AF: 0.812 Hom.: 4465

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11467214; hg19: chr20-35807790;