16-21609226-A-G

Position:

• chr16-21609226-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL9	NM_016025.5	c.166-3419A>G		intron_variant		ENST00000358154.8
METTL9	NM_001077180.3	c.166-3419A>G		intron_variant
METTL9	NM_001288659.2	c.46-3419A>G		intron_variant
METTL9	NM_001288660.2	c.46-3419A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL9	ENST00000358154.8	c.166-3419A>G		intron_variant		1	NM_016025.5	P3

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

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.771

Alfa AF: 0.736 Hom.: 40861

Bravo AF: 0.817

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs226005; hg19: chr16-21620547;