rs11467214

chr20-37179387-G-GCTTACAAACAGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGACACTchr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGAACTchr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTACAGACAGGGCCCGCGGCCGGCACTchr20-37179387-G-GCTTATACACAGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTATAGACAchr20-37179387-G-GCTTATAGACAGGCCCCCGCGGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGCAGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCAGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCATTchr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCGGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGCGGTCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCCGTGGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCGCGGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCGGCGGCCGGCACTchr20-37179387-G-GCTTATAGACAGGGCCCTGCGGCCGGCACTchr20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTATchr20-37179387-G-GCTTATGGACAGGGCCCCGCGGCCGGCACTchr20-37179387-G-GCTTGTAGACAGGGCCCCGCGGCCGGCACT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_152503.8(MROH8):c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG(p.Asn31LysfsTer10) variant causes a splice donor, stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: MROH8 NM_152503.8 splice_donor, stop_gained, frameshift
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_152503.8 Downstream stopcodon found after 781 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH8	NM_152503.8	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		ENST00000710289.2
RPN2	NM_002951.5	c.13+21_13+22insACAAACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		ENST00000237530.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTTTGTAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		1		P2
RPN2	ENST00000237530.11	c.13+21_13+22insACAAACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		1	NM_002951.5	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

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;