1-170167488-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001136107.2(NTMT2):​c.583C>G​(p.His195Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,394,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

NTMT2
NM_001136107.2 missense, splice_region

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.388
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 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity NTM1B_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTMT2NM_001136107.2 linkc.583C>G p.His195Asp missense_variant, splice_region_variant Exon 4 of 4 ENST00000439373.3 NP_001129579.1 Q5VVY1
NTMT2XM_011509232.3 linkc.388C>G p.His130Asp missense_variant, splice_region_variant Exon 5 of 5 XP_011507534.1
NTMT2XM_011509233.3 linkc.388C>G p.His130Asp missense_variant, splice_region_variant Exon 6 of 6 XP_011507535.1
NTMT2XM_011509234.3 linkc.388C>G p.His130Asp missense_variant, splice_region_variant Exon 5 of 5 XP_011507536.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTMT2ENST00000439373.3 linkc.583C>G p.His195Asp missense_variant, splice_region_variant Exon 4 of 4 1 NM_001136107.2 ENSP00000408058.3 Q5VVY1
NTMT2ENST00000367764.3 linkn.641C>G splice_region_variant, non_coding_transcript_exon_variant Exon 5 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000215
AC:
3
AN:
1394036
Hom.:
0
Cov.:
31
AF XY:
0.00000291
AC XY:
2
AN XY:
687100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000385
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.583C>G (p.H195D) alteration is located in exon 4 (coding exon 4) of the METTL11B gene. This alteration results from a C to G substitution at nucleotide position 583, causing the histidine (H) at amino acid position 195 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.35
N
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.38
T
PROVEAN
Pathogenic
-8.3
D
REVEL
Benign
0.22
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.018
D
Polyphen
0.11
B
Vest4
0.43
MutPred
0.85
Gain of ubiquitination at K199 (P = 0.0767);
MVP
0.030
ClinPred
0.99
D
GERP RS
-3.5
Varity_R
0.93
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-170136629; API