Genetic Variant NM_152503.8:c.257+351T>A (chr20-37178902-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152503.8(MROH8):c.257+321T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 152,222 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.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MROH8
NM_152503.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.468

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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	Effect	Exon Rank	Protein	UniProt
MROH8	NM_152503.8	MANE Select	c.257+321T>A	intron	N/A	NP_689716.4
MROH8	NM_213631.3		c.257+321T>A	intron	N/A	NP_998796.1	A0AAG2UW82
MROH8	NM_213632.3		c.257+321T>A	intron	N/A	NP_998797.2	A0AAG2UWF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MROH8	ENST00000343811.10	TSL:1	c.257+321T>A	intron	N/A	ENSP00000513568.1	A0A8V8TLY2
MROH8	ENST00000400440.7	TSL:1	c.257+321T>A	intron	N/A	ENSP00000513569.1	A0A8V8TN72
RPN2	ENST00000705448.1		c.-455A>T	5_prime_UTR	Exon 1 of 18	ENSP00000516126.1	A0A994J5J1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

9708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5288

African (AFR)

AF:

0.00

AC:

AN:

308

American (AMR)

AF:

0.00

AC:

AN:

272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

278

East Asian (EAS)

AF:

0.00

AC:

AN:

396

South Asian (SAS)

AF:

0.00

AC:

AN:

1300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

6324

Other (OTH)

AF:

0.00

AC:

AN:

486

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.2

(source)

DANN

Benign

0.84

PhyloP100

0.47

PromoterAI

-0.072

Neutral

(source)

Splicing

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

Publications

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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