chr20-37112391-T-C

Variant names:

• chr20-37112391-T-C
• rs1744760
• NM_152503.8:c.2747A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152503.8(MROH8):​c.2747A>G​(p.Gln916Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,355,222 control chromosomes in the GnomAD database, including 160,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14492 hom., cov: 32)
  • Exomes 𝑓: 0.49 (146022 hom.)
• Consequence: MROH8 NM_152503.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3868186E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	NM_152503.8	MANE Select	c.2747A>G	p.Gln916Arg	missense	Exon 21 of 25	NP_689716.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	ENST00000343811.10	TSL:1	c.2747A>G	p.Gln916Arg	missense	Exon 21 of 25	ENSP00000513568.1
	MROH8	ENST00000422138.2	TSL:3	c.2489A>G	p.Gln830Arg	missense	Exon 19 of 23	ENSP00000400468.2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63577 AN: 151896 Hom.: 14486 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.472 AC: 112933 AN: 239136 AF XY: 0.481

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.460

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.489 AC: 587827 AN: 1203208 Hom.: 146022 Cov.: 33 AF XY: 0.492 AC XY: 293500 AN XY: 596160

African (AFR) AF: 0.215 AC: 5552 AN: 25850

American (AMR) AF: 0.493 AC: 17360 AN: 35236

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 8634 AN: 16528

East Asian (EAS) AF: 0.469 AC: 7455 AN: 15906

South Asian (SAS) AF: 0.576 AC: 46684 AN: 80984

European-Finnish (FIN) AF: 0.428 AC: 13858 AN: 32414

Middle Eastern (MID) AF: 0.454 AC: 2011 AN: 4428

European-Non Finnish (NFE) AF: 0.491 AC: 465360 AN: 948484

Other (OTH) AF: 0.482 AC: 20913 AN: 43378

GnomAD4 genome AF: 0.418 AC: 63602 AN: 152014 Hom.: 14492 Cov.: 32 AF XY: 0.421 AC XY: 31286 AN XY: 74292

African (AFR) AF: 0.227 AC: 9410 AN: 41512

American (AMR) AF: 0.512 AC: 7816 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2511 AN: 5172

South Asian (SAS) AF: 0.586 AC: 2820 AN: 4816

European-Finnish (FIN) AF: 0.419 AC: 4424 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33313 AN: 67920

Other (OTH) AF: 0.429 AC: 905 AN: 2112

Alfa AF: 0.471 Hom.: 81852

Bravo AF: 0.413

TwinsUK AF: 0.489 AC: 1812

ALSPAC AF: 0.505 AC: 1947

ESP6500AA AF: 0.239 AC: 906

ESP6500EA AF: 0.480 AC: 3955

ExAC AF: 0.477 AC: 57581

Asia WGS AF: 0.522 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Benign	0.40
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.20
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.56	N
REVEL	Benign	0.051
Sift	Benign	0.91	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.034
ClinPred		0.0019	T
GERP RS		-3.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1744760; hg19: chr20-35740794; COSMIC: COSV54118441; COSMIC: COSV54118441;