16-21609226-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016025.5(METTL9):​c.166-3419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,024 control chromosomes in the GnomAD database, including 49,268 homozygotes. 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: 𝑓 0.80 (49268 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

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>G		intron	N/A	NP_057109.3
	METTL9	NM_001077180.3		c.166-3419A>G		intron	N/A	NP_001070648.1	Q9H1A3-2
	METTL9	NM_001288659.2		c.46-3419A>G		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>G		intron	N/A	ENSP00000350874.3	Q9H1A3-1
	METTL9	ENST00000396014.8	TSL:1	c.166-3419A>G		intron	N/A	ENSP00000379335.4	Q9H1A3-2
	METTL9	ENST00000873751.1		c.166-3419A>G		intron	N/A	ENSP00000543810.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121256 AN: 151906 Hom.: 49204 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.798 AC: 121379 AN: 152024 Hom.: 49268 Cov.: 30 AF XY: 0.802 AC XY: 59568 AN XY: 74300

African (AFR) AF: 0.946 AC: 39231 AN: 41486

American (AMR) AF: 0.824 AC: 12594 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2507 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4504 AN: 5168

South Asian (SAS) AF: 0.820 AC: 3945 AN: 4812

European-Finnish (FIN) AF: 0.714 AC: 7538 AN: 10564

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48546 AN: 67936

Other (OTH) AF: 0.771 AC: 1625 AN: 2108

Alfa AF: 0.765 Hom.: 69315

Bravo AF: 0.817

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.57
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs226005;

hg19: chr16-21620547;