NM_152503.8:c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG

Variant names:

• chr20-37179388-C-CCTTACAAACAGGGCCCCGCGGCCGGCACT
• NM_152503.8:c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152503.8(MROH8):​c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG​(p.Asn31fs) variant causes a frameshift, stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 44)
• Consequence: MROH8 NM_152503.8 frameshift, stop_gained, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152503.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	NM_152503.8	MANE Select	c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31fs	frameshift stop_gained splice_region	Exon 1 of 25	NP_689716.4
	RPN2	NM_002951.5	MANE Select	c.13+19_13+20insCTTACAAACAGGGCCCCGCGGCCGGCACT		intron	N/A	NP_002942.2
	MROH8	NM_213631.3		c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31fs	frameshift stop_gained splice_region	Exon 1 of 14	NP_998796.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	ENST00000343811.10	TSL:1	c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31fs	frameshift stop_gained splice_region	Exon 1 of 25	ENSP00000513568.1
	MROH8	ENST00000400440.7	TSL:1	c.92_92+1insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31fs	frameshift stop_gained splice_region	Exon 1 of 14	ENSP00000513569.1
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.13+19_13+20insCTTACAAACAGGGCCCCGCGGCCGGCACT		intron	N/A	ENSP00000237530.6

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0070

Splicing

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

Other links and lift over

hg19: chr20-35807791;