Variant 20-20025758-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_ModeratePM1PM2PP5_Moderate

The NM_016100.5(NAA20):c.160A>G(p.Met54Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NAA20
NM_016100.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.08

Variant links:

Genes affected

NAA20 (HGNC:15908): (N-alpha-acetyltransferase 20, NatB catalytic subunit) NAT5 is a component of N-acetyltransferase complex B (NatB). Human NatB performs cotranslational N(alpha)-terminal acetylation of methionine residues when they are followed by asparagine (Starheim et al., 2008 [PubMed 18570629]).[supplied by OMIM, Apr 2009]

NAA20 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PS1

Transcript NM_016100.5 (NAA20) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM1

In a domain N-acetyltransferase (size 155) in uniprot entity NAA20_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_016100.5

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 20-20025758-A-G is Pathogenic according to our data. Variant chr20-20025758-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1338747.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NAA20	NM_016100.5 linkuse as main transcript	c.160A>G	p.Met54Val	missense_variant	3/6	ENST00000334982.9
NAA20	NM_181527.3 linkuse as main transcript	c.124A>G	p.Met42Val	missense_variant	3/6
NAA20	NM_181528.3 linkuse as main transcript	c.160A>G	p.Met54Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA20	ENST00000334982.9 linkuse as main transcript	c.160A>G	p.Met54Val	missense_variant	3/6	1	NM_016100.5	P1	P61599-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719744

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.12e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual developmental disorder, autosomal recessive 73

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 27, 2022	- -
Likely pathogenic, criteria provided, single submitter	research	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 17, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;.;T

Eigen

Benign

-0.014

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.7

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.088

T;D;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.0060

B;.;B

Vest4

0.81

MutPred

0.48

Gain of phosphorylation at Y56 (P = 0.1683);Gain of phosphorylation at Y56 (P = 0.1683);.;

MVP

0.30

MPC

0.56

ClinPred

0.95

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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