rs17349873

Positions:

• chr1-170151574-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136107.2(NTMT2):​c.154+5313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 153,176 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (82 hom., cov: 31)
  • Exomes 𝑓: 0.012 (2 hom.)
• Consequence: NTMT2 NM_001136107.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTMT2	NM_001136107.2	c.154+5313T>C		intron_variant		ENST00000439373.3
NTMT2	XM_011509232.3	c.-191+5313T>C		intron_variant
NTMT2	XM_011509233.3	c.-209-4295T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTMT2	ENST00000439373.3	c.154+5313T>C		intron_variant		1	NM_001136107.2	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4149 AN: 151988 Hom.: 82 Cov.: 31

Gnomad AFR AF: 0.00803

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00960

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.0121 AC: 13 AN: 1070 Hom.: 2 AF XY: 0.0101 AC XY: 6 AN XY: 596

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0273 AC: 4152 AN: 152106 Hom.: 82 Cov.: 31 AF XY: 0.0255 AC XY: 1897 AN XY: 74340

Gnomad4 AFR AF: 0.00803

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00962

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0301

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0321 Hom.: 15

Bravo AF: 0.0245

Asia WGS AF: 0.0430 AC: 149 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.011
DANN	Benign	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: rs17349873; hg19: chr1-170120715;