rs1178190439

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-37179381-C-G
• chr20-37179381-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_152503.8(MROH8):​c.99G>C​(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 44)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH8 NM_152503.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.094).
• BP6: Variant 20-37179381-C-G is Benign according to our data. Variant chr20-37179381-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2993305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.

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>C	p.Ala33Ala	synonymous	Exon 2 of 25	NP_689716.4
	RPN2	NM_002951.5	MANE Select	c.13+12C>G		intron	N/A	NP_002942.2
	MROH8	NM_213631.3		c.99G>C	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>C	p.Ala33Ala	synonymous	Exon 2 of 25	ENSP00000513568.1	A0A8V8TLY2
	MROH8	ENST00000400440.7	TSL:1	c.99G>C	p.Ala33Ala	synonymous	Exon 2 of 14	ENSP00000513569.1	A0A8V8TN72
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.13+12C>G		intron	N/A	ENSP00000237530.6	P04844-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151692 Hom.: 0 Cov.: 44

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354168 Hom.: 0 Cov.: 80 AF XY: 0.00 AC XY: 0 AN XY: 661678

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

American (AMR) AF: 0.0000295 AC: 1 AN: 33914

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 34256

South Asian (SAS) AF: 0.00 AC: 0 AN: 77472

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052464

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151692 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 74080

African (AFR) AF: 0.00 AC: 0 AN: 41346

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		1.2
PromoterAI		-0.26	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1178190439; hg19: chr20-35807784;