20-37179387-G-GCTTATAGACAGGGCCCGGCGGCCGGCACT

Position:

• chr20-37179387-G-GCTTATAGACAGGGCCCGGCGGCCGGCACT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000343811.10(MROH8):​c.92+1_93insAGTGCCGGCCGCCGGGCCCTGTCTATAAG​(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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: MROH8 ENST00000343811.10 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 20-37179387-G-GCTTATAGACAGGGCCCGGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTATAGACAGGGCCCGGCGGCCGGCACT is described in ClinVar as [Likely_benign]. Clinvar id is 2120293.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH8	NM_152503.8	c.92+1_93insAGTGCCGGCCGCCGGGCCCTGTCTATAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		ENST00000710289.2	NP_689716.4
RPN2	NM_002951.5	c.13+21_13+22insATAGACAGGGCCCGGCGGCCGGCACTCTT		intron_variant		ENST00000237530.11	NP_002942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCCGGGCCCTGTCTATAAG	p.Asn31LysfsTer10	splice_donor_variant, stop_gained, frameshift_variant		1		ENSP00000513568	P2
RPN2	ENST00000237530.11	c.13+21_13+22insATAGACAGGGCCCGGCGGCCGGCACTCTT		intron_variant		1	NM_002951.5	ENSP00000237530	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 0

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 26, 2023

- -

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;