rs368219054

Variant names:

• chr1-170971804-T-G
• rs368219054
• NM_001163629.2:c.537T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001163629.2(MROH9):​c.537T>G​(p.Cys179Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: MROH9 NM_001163629.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0180
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

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.537T>G	p.Cys179Trp	missense	Exon 8 of 22	NP_001157101.1	Q5TGP6-2
	MROH9	NM_025063.4		c.537T>G	p.Cys179Trp	missense	Exon 8 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.537T>G	p.Cys179Trp	missense	Exon 8 of 22	ENSP00000356733.4	Q5TGP6-2
	MROH9	ENST00000367758.7	TSL:1	c.537T>G	p.Cys179Trp	missense	Exon 8 of 15	ENSP00000356732.3	Q5TGP6-1
	MROH9	ENST00000864982.1		c.537T>G	p.Cys179Trp	missense	Exon 8 of 21	ENSP00000535041.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249438 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000122 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00000827 AC: 1

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.018
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.016	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.27
MPC		0.41
ClinPred		0.58	D
GERP RS		-1.3
Varity_R		0.61
gMVP		0.38
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs368219054; hg19: chr1-170940945;