dbSNP rs372307021: NTMT1:p.Thr102Ser (chr9-129634196-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014064.4(NTMT1):c.305C>G(p.Thr102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T102I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NTMT1
NM_014064.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.538

Publications

0 publications found

Variant links:

Genes affected

NTMT1 (HGNC:23373): (N-terminal Xaa-Pro-Lys N-methyltransferase 1) The METTL11A gene encodes an N-terminal methyltransferase for the RAN (MIM 601179) guanine nucleotide exchange factor regulator of chromosome condensation 1 (RCC1; MIM 179710). METTL11A enzyme alpha-N-methylates other protein targets such as SET (MIM 600960) and RB (MIM 180200).[supplied by OMIM, Nov 2010]

NTMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTMT1	NM_014064.4	MANE Select	c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	NP_054783.2	Q9BV86-1
NTMT1	NM_001286796.2		c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	NP_001273725.1	Q9BV86-1
NTMT1	NM_001286797.2		c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	NP_001273726.1	Q9BV86-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTMT1	ENST00000372483.9	TSL:1 MANE Select	c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	ENSP00000361561.4	Q9BV86-1
NTMT1	ENST00000372480.1	TSL:3	c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	ENSP00000361558.1	Q9BV86-1
NTMT1	ENST00000372486.5	TSL:5	c.305C>G	p.Thr102Ser	missense	Exon 3 of 4	ENSP00000361564.1	Q9BV86-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.018

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.64

M_CAP

Benign

0.0033

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

PhyloP100

0.54

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.040

REVEL

Benign

0.11

Sift

Benign

0.49

Sift4G

Benign

0.81

Polyphen

0.0

Vest4

0.10

MutPred

0.39

Gain of disorder (P = 0.0505)

MVP

0.12

MPC

0.41

ClinPred

0.17

GERP RS

4.7

Varity_R

0.30

gMVP

0.26

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over