16-3476241-T-C

Position:

chr16-3476241-T-C

Variant summary

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

The NM_001083601.3(NAA60):c.14T>C(p.Val5Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,458,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAA60
NM_001083601.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

NAA60 (HGNC:25875): (N-alpha-acetyltransferase 60, NatF catalytic subunit) This gene encodes an enzyme that localizes to the Golgi apparatus, where it transfers an acetyl group to the N-terminus of free proteins. This enzyme acts on histones, and its activity is important for chromatin assembly and chromosome integrity. Alternative splicing and the use of alternative promoters results in multiple transcript variants. The upstream promoter is located in a differentially methylated region (DMR) and undergoes imprinting; transcript variants originating from this position are expressed from the maternal allele. [provided by RefSeq, Nov 2015]

NAA60 links:

ENSG00000285329 (HGNC:):

ENSG00000285329 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=0.2039764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3 linkuse as main transcript	c.14T>C	p.Val5Ala	missense_variant	3/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAA60	ENST00000407558.9 linkuse as main transcript	c.14T>C	p.Val5Ala	missense_variant	3/8	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000414063.6 linkuse as main transcript	c.14T>C	p.Val5Ala	missense_variant	2/7	2		ENSP00000393224.2	Q9H7X0-1
NAA60	ENST00000424546.6 linkuse as main transcript	c.132-3230T>C		intron_variant		2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000360862.9 linkuse as main transcript	c.-85-3230T>C		intron_variant		2		ENSP00000354108.5	Q9H7X0-3
NAA60	ENST00000573580.5 linkuse as main transcript	c.-85-3230T>C		intron_variant		4		ENSP00000459055.1	Q9H7X0-3
NAA60	ENST00000572739.5 linkuse as main transcript	n.14T>C		non_coding_transcript_exon_variant	2/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.14T>C		non_coding_transcript_exon_variant	2/5	4		ENSP00000458717.1	I3L1B9
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.*10T>C		non_coding_transcript_exon_variant	4/5	4		ENSP00000477472.1	V9GZ69
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.*10T>C		3_prime_UTR_variant	4/5	4		ENSP00000477472.1	V9GZ69

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152082

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246676

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458302

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725420

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:

0.00000901

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 17, 2023

The c.14T>C (p.V5A) alteration is located in exon 3 (coding exon 1) of the NAA60 gene. This alteration results from a T to C substitution at nucleotide position 14, causing the valine (V) at amino acid position 5 to be replaced by an alanine (A). 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

0.30

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

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

Eigen

Benign

0.026

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.;.;.;.;M;.;M;M;.;M;M;M;.;M;.;M;.;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.076

Sift

Uncertain

0.022

D;.;.;.;.;.;.;.;.;.;D;D;.;.;.;.;.;.;.

Sift4G

Benign

0.091

T;T;T;T;T;.;T;T;.;T;D;T;T;T;D;T;T;T;D

Polyphen

0.73

P;.;.;.;.;P;.;P;P;.;.;P;P;.;.;.;P;.;.

Vest4

0.40

MutPred

0.40

Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);Gain of disorder (P = 0.0806);

MVP

0.043

MPC

0.41

ClinPred

0.43

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

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