chr16-21609685-T-A

Position:

• chr16-21609685-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016025.5(METTL9):​c.166-2960T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 151,924 control chromosomes in the GnomAD database, including 46 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 0.0089 (46 hom., cov: 32)
• Consequence: METTL9 NM_016025.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 (EAS) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL9	NM_016025.5	c.166-2960T>A		intron_variant		ENST00000358154.8	NP_057109.3
METTL9	NM_001077180.3	c.166-2960T>A		intron_variant			NP_001070648.1
METTL9	NM_001288659.2	c.46-2960T>A		intron_variant			NP_001275588.1
METTL9	NM_001288660.2	c.46-2960T>A		intron_variant			NP_001275589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL9	ENST00000358154.8	c.166-2960T>A		intron_variant		1	NM_016025.5	ENSP00000350874	P3

Frequencies

GnomAD3 genomes AF: 0.00889 AC: 1349 AN: 151806 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00385

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

GnomAD4 genome AF: 0.00887 AC: 1348 AN: 151924 Hom.: 46 Cov.: 32 AF XY: 0.0119 AC XY: 880 AN XY: 74254

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.0125

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00339 Hom.: 0

Bravo AF: 0.00431

Asia WGS AF: 0.0710 AC: 246 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	0.34
DANN	Benign	0.35

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: rs155026; hg19: chr16-21621006;