20-37179381-C-T

Variant names:

• chr20-37179381-C-T
• rs1178190439
• NM_152503.8:c.99G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152503.8(MROH8):​c.99G>A​(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,354,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A33A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 44)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MROH8 NM_152503.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.99G>A	p.Ala33Ala	synonymous	Exon 2 of 25	NP_689716.4
	RPN2	NM_002951.5	MANE Select	c.13+12C>T		intron	N/A	NP_002942.2
	MROH8	NM_213631.3		c.99G>A	p.Ala33Ala	synonymous	Exon 2 of 14	NP_998796.1	A0AAG2UW82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	ENST00000343811.10	TSL:1	c.99G>A	p.Ala33Ala	synonymous	Exon 2 of 25	ENSP00000513568.1	A0A8V8TLY2
	MROH8	ENST00000400440.7	TSL:1	c.99G>A	p.Ala33Ala	synonymous	Exon 2 of 14	ENSP00000513569.1	A0A8V8TN72
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.13+12C>T		intron	N/A	ENSP00000237530.6	P04844-1

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD2 exomes AF: 0.00000815 AC: 1 AN: 122756 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1354166 Hom.: 0 Cov.: 80 AF XY: 0.00000453 AC XY: 3 AN XY: 661678

African (AFR) AF: 0.00 AC: 0 AN: 30748

American (AMR) AF: 0.00 AC: 0 AN: 33914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24348

East Asian (EAS) AF: 0.0000292 AC: 1 AN: 34256

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 9.50e-7 AC: 1 AN: 1052464

Other (OTH) AF: 0.00 AC: 0 AN: 56058

GnomAD4 genome Cov.: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		1.2
PromoterAI		0.077	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -2

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

Other links and lift over

dbSNP: rs1178190439; hg19: chr20-35807784;