chr1-170167488-C-G

Variant names:

• chr1-170167488-C-G
• NM_001136107.2:c.583C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001136107.2(NTMT2):​c.583C>G​(p.His195Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,394,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: NTMT2 NM_001136107.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.388
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity NTM1B_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136107.2. 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
	NTMT2	NM_001136107.2	MANE Select	c.583C>G	p.His195Asp	missense splice_region	Exon 4 of 4	NP_001129579.1	Q5VVY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTMT2	ENST00000439373.3	TSL:1 MANE Select	c.583C>G	p.His195Asp	missense splice_region	Exon 4 of 4	ENSP00000408058.3	Q5VVY1
	NTMT2	ENST00000962802.1		c.581-46C>G		intron	N/A	ENSP00000632861.1
	NTMT2	ENST00000367764.3	TSL:5	n.641C>G		splice_region non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1394036 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 687100

African (AFR) AF: 0.00 AC: 0 AN: 31574

American (AMR) AF: 0.00 AC: 0 AN: 35472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24670

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000385 AC: 3 AN: 77996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076232

Other (OTH) AF: 0.00 AC: 0 AN: 57816

GnomAD4 genome Cov.: 31

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.39
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		0.11	B
Vest4		0.43
MutPred		0.85		Gain of ubiquitination at K199 (P = 0.0767)
MVP		0.030
ClinPred		0.99	D
GERP RS		-3.5
Varity_R		0.93
gMVP		0.88
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-170136629;