chr1-171784040-G-A

Variant names:

• chr1-171784040-G-A
• NM_015935.5:c.454G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015935.5(METTL13):​c.454G>A​(p.Val152Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: METTL13 NM_015935.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13
• Publications: 0 publications found

Genes affected

METTL13 (HGNC:24248): (methyltransferase 13, eEF1A N-terminus and K55) Predicted to enable methyltransferase activity. Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL13	NM_015935.5	c.454G>A	p.Val152Met	missense_variant	Exon 2 of 8	ENST00000361735.4	NP_057019.3
METTL13	NM_014955.3	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 8		NP_055770.1
METTL13	NM_001007239.2	c.453+1G>A		splice_donor_variant, intron_variant	Intron 2 of 7		NP_001007240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL13	ENST00000361735.4	c.454G>A	p.Val152Met	missense_variant	Exon 2 of 8	1	NM_015935.5	ENSP00000354920.3
METTL13	ENST00000367737.9	c.453+1G>A		splice_donor_variant, intron_variant	Intron 2 of 7	1		ENSP00000356711.5
METTL13	ENST00000362019.7	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 8	2		ENSP00000355393.3
METTL13	ENST00000485629.1	n.565+1G>A		splice_donor_variant, intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454G>A (p.V152M) alteration is located in exon 2 (coding exon 2) of the METTL13 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the valine (V) at amino acid position 152 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.015	T
PhyloP100		6.1
ClinPred		0.87	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.21
Mutation Taster		=0/100	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr1-171753180;