chr1-170151574-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.00 AC: 0 AN: 28

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 24

European-Finnish (FIN) AF: 0.0199 AC: 8 AN: 402

Middle Eastern (MID) AF: 0.00187 AC: 1 AN: 536

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.0152 AC: 1 AN: 66

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

African (AFR) AF: 0.00803 AC: 334 AN: 41572

American (AMR) AF: 0.0160 AC: 245 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.00962 AC: 49 AN: 5094

South Asian (SAS) AF: 0.0471 AC: 226 AN: 4802

European-Finnish (FIN) AF: 0.0301 AC: 319 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2829 AN: 67956

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

Alfa AF: 0.0316 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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17349873; hg19: chr1-170120715;