Variant 14-57391345-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001011713.3(NAA30):c.388G>T(p.Ala130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,611,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NAA30
NM_001011713.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.226

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016684562).

BS2

High AC in GnomAd4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA30	NM_001011713.3 linkuse as main transcript	c.388G>T	p.Ala130Ser	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.388G>T	p.Ala130Ser	missense_variant	2/5	1	NM_001011713.3	ENSP00000452521.1	Q147X3-1
NAA30	ENST00000298406.6 linkuse as main transcript	c.43G>T	p.Ala15Ser	missense_variant	1/4	1		ENSP00000298406.6	J3KNC2
NAA30	ENST00000554703.1 linkuse as main transcript	c.-4+640G>T		intron_variant		1		ENSP00000451255.1	G3V3I2
NAA30	ENST00000555166.5 linkuse as main transcript	c.-4+640G>T		intron_variant		2		ENSP00000450939.1	B4DK34

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

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:

0.000478

GnomAD3 exomes

AF:

0.0000661

AC:

AN:

242094

Hom.:

AF XY:

0.0000302

AC XY:

AN XY:

132496

show subpopulations

Gnomad AFR exome

AF:

0.000940

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1459680

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726094

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000900

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000355

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000826

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

Apr 13, 2023

The c.388G>T (p.A130S) alteration is located in exon 2 (coding exon 1) of the NAA30 gene. This alteration results from a G to T substitution at nucleotide position 388, causing the alanine (A) at amino acid position 130 to be replaced by a serine (S). 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

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.4

DANN

Benign

0.93

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.56

M_CAP

Benign

0.029

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.21

REVEL

Benign

0.044

Sift

Benign

0.29

Sift4G

Benign

0.66

Polyphen

0.030

Vest4

0.096

MVP

0.35

MPC

0.41

ClinPred

0.016

GERP RS

1.5

Varity_R

0.058

gMVP

0.12

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