1-156734088-T-C

Position:

• chr1-156734088-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000368216.9(METTL25B):​c.716T>C​(p.Leu239Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL25B ENST00000368216.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

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]

METTL25B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL25B	NM_015997.4	c.716T>C	p.Leu239Pro	missense_variant	6/8	ENST00000368216.9	NP_057081.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL25B	ENST00000368216.9	c.716T>C	p.Leu239Pro	missense_variant	6/8	1	NM_015997.4	ENSP00000357199.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.716T>C (p.L239P) alteration is located in exon 6 (coding exon 6) of the RRNAD1 gene. This alteration results from a T to C substitution at nucleotide position 716, causing the leucine (L) at amino acid position 239 to be replaced by a proline (P). 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	0.20
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.24
Sift	Benign	0.036	D;D
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.59		Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.72
MPC		0.95
ClinPred		0.86	D
GERP RS		3.9
Varity_R		0.41
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-156703880;