rs226005

Variant names:

• chr16-21609226-A-C
• rs226005
• NM_016025.5:c.166-3419A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-21609226-A-C
• chr16-21609226-A-G
• chr16-21609226-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016025.5(METTL9):​c.166-3419A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: METTL9 NM_016025.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 18 publications found

Genes affected

METTL9 (HGNC:24586): (methyltransferase 9, His-X-His N1(pi)-histidine) Enables protein-L-histidine N-pros-methyltransferase activity. Predicted to be involved in methylation. Is active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000301756 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016025.5. 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
	METTL9	NM_016025.5	MANE Select	c.166-3419A>C		intron	N/A	NP_057109.3
	METTL9	NM_001077180.3		c.166-3419A>C		intron	N/A	NP_001070648.1	Q9H1A3-2
	METTL9	NM_001288659.2		c.46-3419A>C		intron	N/A	NP_001275588.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL9	ENST00000358154.8	TSL:1 MANE Select	c.166-3419A>C		intron	N/A	ENSP00000350874.3	Q9H1A3-1
	METTL9	ENST00000396014.8	TSL:1	c.166-3419A>C		intron	N/A	ENSP00000379335.4	Q9H1A3-2
	METTL9	ENST00000873751.1		c.166-3419A>C		intron	N/A	ENSP00000543810.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.60
PhyloP100		-0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs226005; hg19: chr16-21620547;