Genetic Variant NTMT2:c.154+5313T>C (chr1-170151574-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

2 publications found

Variant links:

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]

NTMT2 links:

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]

MIR3119-1 links:

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]

MIR3119-2 links:

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ACMG classification

Classification was made for transcript

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 link	c.154+5313T>C		intron_variant	Intron 1 of 3	ENST00000439373.3	NP_001129579.1	Q5VVY1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NTMT2	ENST00000439373.3 link	c.154+5313T>C	intron_variant	Intron 1 of 3	1	NM_001136107.2	ENSP00000408058.3	Q5VVY1
MIR3119-1	ENST00000637673.1 link	n.-112A>G	upstream_gene_variant		6
MIR3119-2	ENST00000577602.1 link	n.*112T>C	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4149

AN:

151988

Hom.:

Cov.:

show subpopulations

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:

AN:

1070

Hom.:

AF XY:

0.0101

AC XY:

AN XY:

596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0199

AC:

AN:

402

Middle Eastern (MID)

AF:

0.00187

AC:

AN:

536

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AF:

0.0152

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0273

AC:

4152

AN:

152106

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1897

AN XY:

74340

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00962

AC:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0416

AC:

2829

AN:

67956

Other (OTH)

AF:

0.0260

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

202

404

606

808

1010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0316

Hom.:

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

(source)

DANN

Benign

0.46

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over