Variant 3-113723423-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025146.4(NAA50):c.264A>G(p.Ile88Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NAA50
NM_025146.4 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

NAA50 (HGNC:29533): (N-alpha-acetyltransferase 50, NatE catalytic subunit) Enables H4 histone acetyltransferase activity; peptide alpha-N-acetyltransferase activity; and peptidyl-lysine acetyltransferase activity. Involved in N-terminal protein amino acid acetylation; establishment of mitotic sister chromatid cohesion; and mitotic sister chromatid cohesion, centromeric. Located in cytosol and nucleus. Part of NatA complex. [provided by Alliance of Genome Resources, Apr 2022]

NAA50 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA50	NM_025146.4 linkuse as main transcript	c.264A>G	p.Ile88Met	missense_variant, splice_region_variant	3/5	ENST00000240922.8
NAA50	NM_001308445.2 linkuse as main transcript	c.261A>G	p.Ile87Met	missense_variant, splice_region_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA50	ENST00000240922.8 linkuse as main transcript	c.264A>G	p.Ile88Met	missense_variant, splice_region_variant	3/5	1	NM_025146.4	P4	Q9GZZ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447132

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719770

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:

0.00000271

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

Dec 03, 2021

The c.264A>G (p.I88M) alteration is located in exon 3 (coding exon 3) of the NAA50 gene. This alteration results from a A to G substitution at nucleotide position 264, causing the isoleucine (I) at amino acid position 88 to be replaced by a methionine (M). 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

0.75

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;.;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;.;D;D

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.5

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

0.16

B;.;.;.

Vest4

0.83

MutPred

0.75

Loss of catalytic residue at I88 (P = 0.0368);.;.;.;

MVP

0.65

MPC

1.6

ClinPred

0.98

GERP RS

3.1

Varity_R

0.85

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.24

Position offset: -1

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