Variant chr1-170167488-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000439373.3(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
ENST00000439373.3 missense, splice_region

Scores

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]

NTMT2 links:

NTMT2 (HGNC:):

NTMT2 links:

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/exons	MANE	Protein	UniProt
NTMT2	NM_001136107.2 linkuse as main transcript	c.583C>G	p.His195Asp	missense_variant, splice_region_variant	4/4	ENST00000439373.3	NP_001129579.1	Q5VVY1
NTMT2	XM_011509232.3 linkuse as main transcript	c.388C>G	p.His130Asp	missense_variant, splice_region_variant	5/5		XP_011507534.1
NTMT2	XM_011509233.3 linkuse as main transcript	c.388C>G	p.His130Asp	missense_variant, splice_region_variant	6/6		XP_011507535.1
NTMT2	XM_011509234.3 linkuse as main transcript	c.388C>G	p.His130Asp	missense_variant, splice_region_variant	5/5		XP_011507536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3 linkuse as main transcript	c.583C>G	p.His195Asp	missense_variant, splice_region_variant	4/4	1	NM_001136107.2	ENSP00000408058.3		Q5VVY1
NTMT2	ENST00000367764.3 linkuse as main transcript	n.641C>G		splice_region_variant, non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1394036

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.96

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-8.3

REVEL

Benign

0.22

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.018

Polyphen

0.11

Vest4

0.43

MutPred

0.85

Gain of ubiquitination at K199 (P = 0.0767);

MVP

0.030

ClinPred

0.99

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over