NM_015997.4:c.129C>A

Variant names:

• chr1-156732008-C-A
• NM_015997.4:c.129C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015997.4(METTL25B):​c.129C>A​(p.Asn43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL25B NM_015997.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.112
• Publications: 0 publications found

Genes affected

METTL25B (HGNC:24273): (methyltransferase like 25B) Predicted to enable rRNA (adenine-N6,N6-)-dimethyltransferase activity. Predicted to be involved in rRNA methylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1144492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015997.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL25B	NM_015997.4	MANE Select	c.129C>A	p.Asn43Lys	missense	Exon 2 of 8	NP_057081.3
	METTL25B	NM_001142560.2		c.129C>A	p.Asn43Lys	missense	Exon 2 of 7	NP_001136032.1	Q96FB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL25B	ENST00000368216.9	TSL:1 MANE Select	c.129C>A	p.Asn43Lys	missense	Exon 2 of 8	ENSP00000357199.4	Q96FB5-1
	METTL25B	ENST00000917461.1		c.129C>A	p.Asn43Lys	missense	Exon 2 of 8	ENSP00000587520.1
	METTL25B	ENST00000892486.1		c.129C>A	p.Asn43Lys	missense	Exon 2 of 8	ENSP00000562545.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.11
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.030
Sift	Benign	0.20	T
Sift4G	Benign	0.28	T
Polyphen		0.014	B
Vest4		0.42
MutPred		0.42		Gain of ubiquitination at N43 (P = 0.0177)
MVP		0.20
MPC		0.22
ClinPred		0.22	T
GERP RS		2.6
PromoterAI		-0.0011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.28
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-156701800;