1-170959590-A-G

Variant names:

• chr1-170959590-A-G
• NM_001163629.2:c.281A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001163629.2(MROH9):​c.281A>G​(p.Asp94Gly) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D94N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MROH9 NM_001163629.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 0 publications found

Genes affected

MROH9 (HGNC:26287): (maestro heat like repeat family member 9)

FMO1-AS1 (HGNC:40240):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34133697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163629.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH9	NM_001163629.2	MANE Select	c.281A>G	p.Asp94Gly	missense	Exon 5 of 22	NP_001157101.1	Q5TGP6-2
	MROH9	NM_025063.4		c.281A>G	p.Asp94Gly	missense	Exon 5 of 15	NP_079339.2	Q5TGP6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH9	ENST00000367759.9	TSL:5 MANE Select	c.281A>G	p.Asp94Gly	missense	Exon 5 of 22	ENSP00000356733.4	Q5TGP6-2
	MROH9	ENST00000367758.7	TSL:1	c.281A>G	p.Asp94Gly	missense	Exon 5 of 15	ENSP00000356732.3	Q5TGP6-1
	MROH9	ENST00000864982.1		c.281A>G	p.Asp94Gly	missense	Exon 5 of 21	ENSP00000535041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.0047	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.053
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.17
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.40		Loss of stability (P = 0.1014)
MVP		0.70
MPC		0.39
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.25
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr1-170928731;