20-37178722-C-T

Variant names:

• chr20-37178722-C-T
• rs2880502
• NM_152503.8:c.257+501G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152503.8(MROH8):​c.257+501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH8 NM_152503.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.257+501G>A		intron	N/A	NP_689716.4
	MROH8	NM_213631.3		c.257+501G>A		intron	N/A	NP_998796.1	A0AAG2UW82
	MROH8	NM_213632.3		c.257+501G>A		intron	N/A	NP_998797.2	A0AAG2UWF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	ENST00000343811.10	TSL:1	c.257+501G>A		intron	N/A	ENSP00000513568.1	A0A8V8TLY2
	MROH8	ENST00000400440.7	TSL:1	c.257+501G>A		intron	N/A	ENSP00000513569.1	A0A8V8TN72
	RPN2	ENST00000705448.1		c.-635C>T		5_prime_UTR	Exon 1 of 18	ENSP00000516126.1	A0A994J5J1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 346 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 284

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		0.56
PromoterAI		-0.0088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2880502; hg19: chr20-35807125;