rs971972758

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152503.8(MROH8):c.112C>T(p.Arg38Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

MROH8
NM_152503.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

1 publications found

Variant links:

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]

MROH8 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2892468).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH8	NM_152503.8	MANE Select	c.112C>T	p.Arg38Trp	missense	Exon 2 of 25	NP_689716.4
RPN2	NM_002951.5	MANE Select	c.12G>A	p.Pro4Pro	splice_region synonymous	Exon 1 of 17	NP_002942.2
MROH8	NM_213631.3		c.112C>T	p.Arg38Trp	missense	Exon 2 of 14	NP_998796.1	A0AAG2UW82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MROH8	ENST00000343811.10	TSL:1	c.112C>T	p.Arg38Trp	missense	Exon 2 of 25	ENSP00000513568.1	A0A8V8TLY2
MROH8	ENST00000400440.7	TSL:1	c.112C>T	p.Arg38Trp	missense	Exon 2 of 14	ENSP00000513569.1	A0A8V8TN72
RPN2	ENST00000237530.11	TSL:1 MANE Select	c.12G>A	p.Pro4Pro	splice_region synonymous	Exon 1 of 17	ENSP00000237530.6	P04844-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000659

AC:

AN:

15186

AF XY:

0.000117

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000930

AC:

AN:

322750

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

162800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7508

American (AMR)

AF:

0.00

AC:

AN:

9052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7346

East Asian (EAS)

AF:

0.0000797

AC:

AN:

12554

South Asian (SAS)

AF:

0.00

AC:

AN:

18592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1084

European-Non Finnish (NFE)

AF:

0.00000835

AC:

AN:

239486

Other (OTH)

AF:

0.00

AC:

AN:

14776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

PhyloP100

2.7

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.20

MutPred

0.35

Gain of catalytic residue at L36 (P = 0.0032)

MVP

0.35

ClinPred

0.93

GERP RS

4.6

PromoterAI

-0.42

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=43/57

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over