rs17349873

Variant names:

• chr1-170151574-T-C
• rs17349873
• NM_001136107.2:c.154+5313T>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]

MIR3119-1 (HGNC:38253): (microRNA 3119-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3119-2 (HGNC:38315): (microRNA 3119-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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 rank	MANE	Protein	UniProt
NTMT2	NM_001136107.2	c.154+5313T>C		intron_variant	Intron 1 of 3	ENST00000439373.3	NP_001129579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3	c.154+5313T>C		intron_variant	Intron 1 of 3	1	NM_001136107.2	ENSP00000408058.3
MIR3119-1	ENST00000637673.1	n.-112A>G		upstream_gene_variant		6
MIR3119-2	ENST00000577602.1	n.*112T>C		downstream_gene_variant		6

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;