rs1744760

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-37112391-T-A
• chr20-37112391-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000343811.10(MROH8):​c.2747A>T​(p.Gln916Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH8 ENST00000343811.10 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19336933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.2747A>T	p.Gln916Leu	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>T	p.Gln916Leu	missense_variant	Exon 21 of 25	1		ENSP00000513568.1
MROH8	ENST00000422138.2	c.2489A>T	p.Gln830Leu	missense_variant	Exon 19 of 23	3		ENSP00000400468.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1205310 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 597288

African (AFR) AF: 0.00 AC: 0 AN: 25914

American (AMR) AF: 0.00 AC: 0 AN: 35512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16608

East Asian (EAS) AF: 0.00 AC: 0 AN: 15978

South Asian (SAS) AF: 0.00 AC: 0 AN: 81362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949520

Other (OTH) AF: 0.00 AC: 0 AN: 43504

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 81852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.20
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.093
Sift	Benign	0.084	T
Sift4G	Benign	0.090	T
Polyphen		0.45	P
Vest4		0.45
MutPred		0.46		Loss of methylation at K913 (P = 0.0394);
MVP		0.36
ClinPred		0.74	D
GERP RS		-3.3
Mutation Taster		=91/9	polymorphism

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;