1-156732008-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL25B	NM_015997.4	c.129C>A	p.Asn43Lys	missense_variant	Exon 2 of 8	ENST00000368216.9	NP_057081.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL25B	ENST00000368216.9	c.129C>A	p.Asn43Lys	missense_variant	Exon 2 of 8	1	NM_015997.4	ENSP00000357199.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.129C>A (p.N43K) alteration is located in exon 2 (coding exon 2) of the RRNAD1 gene. This alteration results from a C to A substitution at nucleotide position 129, causing the asparagine (N) at amino acid position 43 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	.;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T;T;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.014	.;B;.
Vest4		0.42
MutPred		0.42		Gain of ubiquitination at N43 (P = 0.0177);Gain of ubiquitination at N43 (P = 0.0177);Gain of ubiquitination at N43 (P = 0.0177);
MVP		0.20
MPC		0.22
ClinPred		0.22	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156701800;