1-156733452-G-A

Variant names:

• chr1-156733452-G-A
• NM_015997.4:c.568G>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.568G>A​(p.Glu190Lys) 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. 16/22 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: 0.294
• 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=0.120167255).

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.568G>A	p.Glu190Lys	missense	Exon 5 of 8	NP_057081.3
	METTL25B	NM_001142560.2		c.568G>A	p.Glu190Lys	missense	Exon 5 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.568G>A	p.Glu190Lys	missense	Exon 5 of 8	ENSP00000357199.4	Q96FB5-1
	METTL25B	ENST00000917461.1		c.520G>A	p.Glu174Lys	missense	Exon 5 of 8	ENSP00000587520.1
	METTL25B	ENST00000892486.1		c.568G>A	p.Glu190Lys	missense	Exon 5 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	0.079
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L
PhyloP100		0.29
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.034
Sift	Benign	0.63	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.42		Gain of MoRF binding (P = 0.0017)
MVP		0.48
MPC		0.21
ClinPred		0.075	T
GERP RS		2.8
Varity_R		0.040
gMVP		0.30
Mutation Taster		=88/12	polymorphism

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

hg19: chr1-156703244;