chr20-37179368-G-C

Variant names:

• chr20-37179368-G-C
• rs971972758
• NM_152503.8:c.112C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152503.8(MROH8):​c.112C>G​(p.Arg38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: MROH8 NM_152503.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08254418).

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.112C>G	p.Arg38Gly	missense	Exon 2 of 25	NP_689716.4
	RPN2	NM_002951.5	MANE Select	c.12G>C	p.Pro4Pro	splice_region synonymous	Exon 1 of 17	NP_002942.2
	MROH8	NM_213631.3		c.112C>G	p.Arg38Gly	missense	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.112C>G	p.Arg38Gly	missense	Exon 2 of 25	ENSP00000513568.1	A0A8V8TLY2
	MROH8	ENST00000400440.7	TSL:1	c.112C>G	p.Arg38Gly	missense	Exon 2 of 14	ENSP00000513569.1	A0A8V8TN72
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.12G>C	p.Pro4Pro	splice_region synonymous	Exon 1 of 17	ENSP00000237530.6	P04844-1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 4 AN: 1748 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00448

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: 0.00258

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000329 AC: 5 AN: 15186 AF XY: 0.000352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000339

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000547

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.000452 AC: 146 AN: 322750 Hom.: 0 Cov.: 4 AF XY: 0.000387 AC XY: 63 AN XY: 162800

African (AFR) AF: 0.00 AC: 0 AN: 7508

American (AMR) AF: 0.000110 AC: 1 AN: 9052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7346

East Asian (EAS) AF: 0.00 AC: 0 AN: 12554

South Asian (SAS) AF: 0.00 AC: 0 AN: 18592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1084

European-Non Finnish (NFE) AF: 0.000589 AC: 141 AN: 239486

Other (OTH) AF: 0.000271 AC: 4 AN: 14776

GnomAD4 genome AF: 0.00229 AC: 4 AN: 1748 Hom.: 0 Cov.: 0 AF XY: 0.00222 AC XY: 2 AN XY: 902

African (AFR) AF: 0.00448 AC: 2 AN: 446

American (AMR) AF: 0.00 AC: 0 AN: 168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 62

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 162

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

European-Non Finnish (NFE) AF: 0.00258 AC: 2 AN: 776

Other (OTH) AF: 0.00 AC: 0 AN: 36

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.25
ClinPred		0.28	T
GERP RS		4.6
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=53/47	polymorphism

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: rs971972758; hg19: chr20-35807771;