rs1489799000

Variant names:

• chr9-129632763-G-T
• rs1489799000
• NM_014064.4:c.60G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-129632763-G-T
• chr9-129632763-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014064.4(NTMT1):​c.60G>T​(p.Trp20Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTMT1 NM_014064.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46
• Publications: 0 publications found

Genes affected

NTMT1 (HGNC:23373): (N-terminal Xaa-Pro-Lys N-methyltransferase 1) The METTL11A gene encodes an N-terminal methyltransferase for the RAN (MIM 601179) guanine nucleotide exchange factor regulator of chromosome condensation 1 (RCC1; MIM 179710). METTL11A enzyme alpha-N-methylates other protein targets such as SET (MIM 600960) and RB (MIM 180200).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014064.4. 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
	NTMT1	NM_014064.4	MANE Select	c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	NP_054783.2	Q9BV86-1
	NTMT1	NM_001286796.2		c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	NP_001273725.1	Q9BV86-1
	NTMT1	NM_001286797.2		c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	NP_001273726.1	Q9BV86-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTMT1	ENST00000372483.9	TSL:1 MANE Select	c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	ENSP00000361561.4	Q9BV86-1
	NTMT1	ENST00000372480.1	TSL:3	c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	ENSP00000361558.1	Q9BV86-1
	NTMT1	ENST00000372486.5	TSL:5	c.60G>T	p.Trp20Cys	missense	Exon 2 of 4	ENSP00000361564.1	Q9BV86-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

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	0.99
PhyloP100		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.99
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1489799000; hg19: chr9-132395042;