1-170146120-G-C

Position:

• chr1-170146120-G-C

Variant summary

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

The ENST00000439373.3(NTMT2):​c.13G>C​(p.Gly5Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NTMT2 ENST00000439373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.94

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=0.21833307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTMT2	NM_001136107.2	c.13G>C	p.Gly5Arg	missense_variant	1/4	ENST00000439373.3	NP_001129579.1
NTMT2	XM_011509232.3	c.-332G>C		5_prime_UTR_variant	1/5		XP_011507534.1
NTMT2	XM_011509233.3	c.-351G>C		5_prime_UTR_variant	1/6		XP_011507535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3	c.13G>C	p.Gly5Arg	missense_variant	1/4	1	NM_001136107.2	ENSP00000408058	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Marfanoid habitus and intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	0.97	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.27	T
Polyphen		0.020	B
Vest4		0.21
MutPred		0.33		Loss of sheet (P = 0.003);
MVP		0.30
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.66

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: rs1571813658; hg19: chr1-170115261;