20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT

Position:

• chr20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The NM_152503.8(MROH8):​c.92+1_93insAGTGCCGGCCGCGGGGCCCCGTCTATAAG variant causes a splice acceptor, splice donor, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH8 NM_152503.8 splice_acceptor, splice_donor, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659

Genes affected

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]

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.052412912 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.7, offset of -29, new splice context is: cgacagccctctccccaaAGagt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant 20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT is described in ClinVar as [Likely_benign]. Clinvar id is 2041031.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPN2	NM_002951.5	c.13+21_13+22insATAGACGGGGCCCCGCGGCCGGCACTCTT		intron_variant		ENST00000237530.11	NP_002942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11	c.13+21_13+22insATAGACGGGGCCCCGCGGCCGGCACTCTT		intron_variant		1	NM_002951.5	ENSP00000237530.6
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCGGGGCCCCGTCTATAAG		splice_acceptor_variant, splice_donor_variant, intron_variant		1		ENSP00000513568.1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 191 AN: 151892 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00437

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00287

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00201 AC: 2730 AN: 1355842 Hom.: 3 Cov.: 83 AF XY: 0.00201 AC XY: 1335 AN XY: 663770

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00208

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00375

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00126 AC: 191 AN: 152008 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 80 AN XY: 74302

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00437

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00134 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

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;