rs777625873

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136107.2(NTMT2):​c.272T>A​(p.Ile91Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000322 in 1,551,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I91T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

NTMT2
NM_001136107.2 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31612366).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTMT2NM_001136107.2 linkc.272T>A p.Ile91Asn missense_variant Exon 2 of 4 ENST00000439373.3 NP_001129579.1 Q5VVY1
NTMT2XM_011509232.3 linkc.77T>A p.Ile26Asn missense_variant Exon 3 of 5 XP_011507534.1
NTMT2XM_011509233.3 linkc.77T>A p.Ile26Asn missense_variant Exon 4 of 6 XP_011507535.1
NTMT2XM_011509234.3 linkc.77T>A p.Ile26Asn missense_variant Exon 3 of 5 XP_011507536.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTMT2ENST00000439373.3 linkc.272T>A p.Ile91Asn missense_variant Exon 2 of 4 1 NM_001136107.2 ENSP00000408058.3 Q5VVY1
NTMT2ENST00000367764.3 linkn.267T>A non_coding_transcript_exon_variant Exon 2 of 5 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000639
AC:
1
AN:
156484
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
82824
show subpopulations
Gnomad AFR exome
AF:
0.000125
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399038
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
690000
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0030
T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.42
T
PROVEAN
Benign
1.6
N
REVEL
Benign
0.054
Sift
Benign
0.083
T
Sift4G
Benign
0.48
T
Polyphen
0.86
P
Vest4
0.56
MVP
0.11
ClinPred
0.24
T
GERP RS
4.6
Varity_R
0.52
gMVP
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777625873; hg19: chr1-170129776; API