rs6442522

Variant names:

• chr3-15399049-C-T
• rs6442522
• ENST00000443029.5:c.*11+12196G>A

Variant summary

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

The ENST00000443029.5(METTL6):​c.*11+12196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,894 control chromosomes in the GnomAD database, including 21,809 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 0.53 (21809 hom., cov: 30)
• Consequence: METTL6 ENST00000443029.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 13 publications found

Genes affected

METTL6 (HGNC:28343): (methyltransferase 6, tRNA N3-cytidine) Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL6	ENST00000443029.5	TSL:5	c.*11+12196G>A		intron	N/A	ENSP00000407613.1
	METTL6	ENST00000458728.5	TSL:3	c.278-14862G>A		intron	N/A	ENSP00000400885.1
	METTL6	ENST00000584799.1	TSL:2	n.104+339G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80012 AN: 151774 Hom.: 21763 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.527 AC: 80118 AN: 151894 Hom.: 21809 Cov.: 30 AF XY: 0.523 AC XY: 38804 AN XY: 74200

African (AFR) AF: 0.658 AC: 27245 AN: 41422

American (AMR) AF: 0.505 AC: 7704 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1890 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3008 AN: 5150

South Asian (SAS) AF: 0.468 AC: 2250 AN: 4812

European-Finnish (FIN) AF: 0.370 AC: 3908 AN: 10552

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32254 AN: 67934

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.503 Hom.: 43295

Bravo AF: 0.544

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.24
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

Other links and lift over

dbSNP: rs6442522; hg19: chr3-15440556;