rs7589845

Positions:

• chr2-169815974-G-A
• chr2-169815974-G-C

Variant summary

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

The NM_014168.4(METTL5):​c.490-446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,004 control chromosomes in the GnomAD database, including 2,956 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 0.19 (2956 hom., cov: 32)
• Consequence: METTL5 NM_014168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

Genes affected

METTL5 (HGNC:25006): (methyltransferase 5, N6-adenosine) Enables S-adenosyl-L-methionine binding activity and rRNA (adenine-N6-)-methyltransferase activity. Involved in positive regulation of translation and rRNA methylation. Located in nucleus; postsynapse; and presynapse. Implicated in autosomal recessive intellectual developmental disorder-72. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL5	NM_014168.4	c.490-446C>T		intron_variant		ENST00000260953.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL5	ENST00000260953.10	c.490-446C>T		intron_variant		1	NM_014168.4	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28486 AN: 151886 Hom.: 2955 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.188 AC: 28501 AN: 152004 Hom.: 2956 Cov.: 32 AF XY: 0.192 AC XY: 14233 AN XY: 74268

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.172

Alfa AF: 0.107 Hom.: 224

Bravo AF: 0.184

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.47

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: rs7589845; hg19: chr2-170672484;