1-170146249-A-G

Variant names:

• chr1-170146249-A-G
• rs1672962860
• NM_001136107.2:c.142A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136107.2(NTMT2):​c.142A>G​(p.Lys48Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NTMT2 NM_001136107.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

NTMT2 (HGNC:31932): (N-terminal Xaa-Pro-Lys N-methyltransferase 2) Enables N-terminal protein N-methyltransferase activity. Involved in N-terminal protein amino acid methylation. Located in nucleus. [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=0.122969955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTMT2	NM_001136107.2	c.142A>G	p.Lys48Glu	missense_variant	Exon 1 of 4	ENST00000439373.3	NP_001129579.1
NTMT2	XM_011509232.3	c.-203A>G		5_prime_UTR_variant	Exon 1 of 5		XP_011507534.1
NTMT2	XM_011509233.3	c.-222A>G		5_prime_UTR_variant	Exon 1 of 6		XP_011507535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3	c.142A>G	p.Lys48Glu	missense_variant	Exon 1 of 4	1	NM_001136107.2	ENSP00000408058.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398900 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689936

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142A>G (p.K48E) alteration is located in exon 1 (coding exon 1) of the METTL11B gene. This alteration results from a A to G substitution at nucleotide position 142, causing the lysine (K) at amino acid position 48 to be replaced by a glutamic acid (E). 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	0.089
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.093
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.061
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.019	D
Polyphen		0.0	B
Vest4		0.32
MutPred		0.26		Loss of ubiquitination at K48 (P = 0.0183);
MVP		0.040
ClinPred		0.83	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1672962860; hg19: chr1-170115390;