9-129635439-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014064.4(NTMT1):c.647A>G(p.His216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

NTMT1
NM_014064.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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:

ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

ASB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19684172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTMT1	NM_014064.4 link	c.647A>G	p.His216Arg	missense_variant	Exon 4 of 4	ENST00000372483.9	NP_054783.2	Q9BV86-1A0A024R8E4
ASB6	NM_017873.4 link	c.*2351T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000277458.5	NP_060343.1	Q9NWX5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTMT1	ENST00000372483.9 link	c.647A>G	p.His216Arg	missense_variant	Exon 4 of 4	1	NM_014064.4	ENSP00000361561.4		Q9BV86-1
ASB6	ENST00000277458 link	c.*2351T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_017873.4	ENSP00000277458.4		Q9NWX5-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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:

0.0000121

AC:

AN:

248214

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134410

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

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

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.647A>G (p.H216R) alteration is located in exon 4 (coding exon 3) of the NTMT1 gene. This alteration results from a A to G substitution at nucleotide position 647, causing the histidine (H) at amino acid position 216 to be replaced by an arginine (R). 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

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;T;T;T;T;T;T

Eigen

Benign

-0.077

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

.;.;T;T;.;.;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.20

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

L;L;.;L;L;.;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.020

N;.;.;.;N;.;N

REVEL

Benign

0.16

Sift

Benign

0.15

T;.;.;.;T;.;T

Sift4G

Benign

0.15

T;T;T;T;T;T;T

Polyphen

0.088

B;B;.;B;B;.;B

Vest4

0.50

MVP

0.17

MPC

0.62

ClinPred

0.12

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.74

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