Variant chr14-57391465-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001011713.3(NAA30):c.508G>A(p.Ala170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,942 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: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NAA30
NM_001011713.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

NAA30 (HGNC:19844): (N-alpha-acetyltransferase 30, NatC catalytic subunit) Enables peptide alpha-N-acetyltransferase activity. Involved in N-terminal peptidyl-methionine acetylation. Located in cytosol and nucleus. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

NAA30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061009318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA30	NM_001011713.3 linkuse as main transcript	c.508G>A	p.Ala170Thr	missense_variant	2/5	ENST00000556492.6	NP_001011713.2	Q147X3-1B3KS28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAA30	ENST00000556492.6 linkuse as main transcript	c.508G>A	p.Ala170Thr	missense_variant	2/5	1	NM_001011713.3	ENSP00000452521.1	Q147X3-1
NAA30	ENST00000298406.6 linkuse as main transcript	c.163G>A	p.Ala55Thr	missense_variant	1/4	1		ENSP00000298406.6	J3KNC2
NAA30	ENST00000554703.1 linkuse as main transcript	c.-4+760G>A		intron_variant		1		ENSP00000451255.1	G3V3I2
NAA30	ENST00000555166.5 linkuse as main transcript	c.-4+760G>A		intron_variant		2		ENSP00000450939.1	B4DK34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240434

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458942

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

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

Dec 05, 2022

The c.508G>A (p.A170T) alteration is located in exon 2 (coding exon 1) of the NAA30 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the alanine (A) at amino acid position 170 to be replaced by a threonine (T). 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

0.086

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.35

REVEL

Benign

0.14

Sift

Benign

0.031

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.11

MutPred

0.16

Gain of glycosylation at A170 (P = 0.0173);

MVP

0.28

MPC

0.43

ClinPred

0.14

GERP RS

0.64

Varity_R

0.058

gMVP

0.26

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