chr20-37112391-T-C

Variant names:

• chr20-37112391-T-C
• rs1744760
• ENST00000343811.10:c.2747A>G

Variant summary

Our verdict is Benign. Variant got -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. 11/13 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.2747A>G	p.Gln916Arg	missense_variant	Exon 21 of 25		NP_689716.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.2747A>G	p.Gln916Arg	missense_variant	Exon 21 of 25	1		ENSP00000513568.1
MROH8	ENST00000422138.2	c.2489A>G	p.Gln830Arg	missense_variant	Exon 19 of 23	3		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

GnomAD3 exomes AF: 0.472 AC: 112933 AN: 239136 Hom.: 27484 AF XY: 0.481 AC XY: 62565 AN XY: 130086

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 SAS exome AF: 0.574

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

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.482

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

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.429

Alfa AF: 0.481 Hom.: 42508

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 v4.3

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
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

Splicing

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

Publications

LitVar

Other links and lift over

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