Variant 1-170146159-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000439373.3(NTMT2):c.52G>C(p.Asp18His) variant causes a missense change. The variant allele was found at a frequency of 0.000601 in 1,551,372 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D18E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00061 ( 6 hom. )

Consequence

NTMT2
ENST00000439373.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034626424).

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NTMT2	NM_001136107.2 linkuse as main transcript	c.52G>C	p.Asp18His	missense_variant	1/4	ENST00000439373.3	NP_001129579.1
NTMT2	XM_011509232.3 linkuse as main transcript	c.-293G>C		5_prime_UTR_variant	1/5		XP_011507534.1
NTMT2	XM_011509233.3 linkuse as main transcript	c.-312G>C		5_prime_UTR_variant	1/6		XP_011507535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTMT2	ENST00000439373.3 linkuse as main transcript	c.52G>C	p.Asp18His	missense_variant	1/4	1	NM_001136107.2	ENSP00000408058	P1

Frequencies

GnomAD3 genomes

AF:

0.000567

AC:

AN:

151740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000626

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00101

AC:

159

AN:

157502

Hom.:

AF XY:

0.000938

AC XY:

AN XY:

83144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000396

Gnomad FIN exome

AF:

0.0000591

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00699

GnomAD4 exome

AF:

0.000605

AC:

847

AN:

1399514

Hom.:

Cov.:

AF XY:

0.000616

AC XY:

425

AN XY:

690240

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00179

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000215

Gnomad4 FIN exome

AF:

0.000121

Gnomad4 NFE exome

AF:

0.000465

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000560

AC:

AN:

151858

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000626

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000692

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000750

Hom.:

Bravo

AF:

0.000816

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000471

AC:

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 19, 2024

The c.52G>C (p.D18H) alteration is located in exon 1 (coding exon 1) of the METTL11B gene. This alteration results from a G to C substitution at nucleotide position 52, causing the aspartic acid (D) at amino acid position 18 to be replaced by a histidine (H). 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

0.61

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.020

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.56

MVP

0.076

ClinPred

0.056

GERP RS

4.2

Varity_R

0.51

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over