Variant chr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGCACT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBA1

The NM_152503.8(MROH8):c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTGTAAG variant causes a splice acceptor, splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,507,316 control chromosomes in the GnomAD database, including 30,895 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2974 hom., cov: 0)

Exomes 𝑓: 0.19 ( 27921 hom. )

Consequence

MROH8
NM_152503.8 splice_acceptor, splice_donor, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.659

Variant links:

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]

RPN2 links:

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]

MROH8 links:

RPN2 (HGNC:):

RPN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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-GCTTACAGACAGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGCACT is described in ClinVar as [Likely_benign]. Clinvar id is 1148510.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPN2	NM_002951.5 linkuse as main transcript	c.13+21_13+22insACAGACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		ENST00000237530.11	NP_002942.2	P04844-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11 linkuse as main transcript	c.13+21_13+22insACAGACAGGGCCCCGCGGCCGGCACTCTT		intron_variant		1	NM_002951.5	ENSP00000237530.6		P04844-1
MROH8	ENST00000343811.10 linkuse as main transcript	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTGTAAG		splice_acceptor_variant, splice_donor_variant, intron_variant		1		ENSP00000513568.1		A0A8V8TLY2

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25766

AN:

151848

Hom.:

2972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0579

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.194

AC:

263244

AN:

1355352

Hom.:

27921

Cov.:

AF XY:

0.196

AC XY:

130220

AN XY:

663504

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.170

AC:

25790

AN:

151964

Hom.:

2974

Cov.:

AF XY:

0.177

AC XY:

13148

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.480

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.177

Hom.:

4465

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over