chr16-3476336-G-A

Position:

chr16-3476336-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001083601.3(NAA60):c.109G>A(p.Glu37Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NAA60
NM_001083601.3 missense, splice_region

Scores

Splicing: ADA: 0.9649

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.38

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a mutagenesis_site Only slightly affects acetyltransferase activity. (size 0) in uniprot entity NAA60_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant, splice_region_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.109G>A	p.Glu37Lys	missense_variant, splice_region_variant	3/8	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000414063.6 linkuse as main transcript	c.109G>A	p.Glu37Lys	missense_variant, splice_region_variant	2/7	2		ENSP00000393224.2	Q9H7X0-1
NAA60	ENST00000424546.6 linkuse as main transcript	c.132-3135G>A		intron_variant		2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000360862.9 linkuse as main transcript	c.-85-3135G>A		intron_variant		2		ENSP00000354108.5	Q9H7X0-3
NAA60	ENST00000573580.5 linkuse as main transcript	c.-85-3135G>A		intron_variant		4		ENSP00000459055.1	Q9H7X0-3
NAA60	ENST00000572739.5 linkuse as main transcript	n.109G>A		splice_region_variant, non_coding_transcript_exon_variant	2/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.109G>A		splice_region_variant, non_coding_transcript_exon_variant	2/5	4		ENSP00000458717.1	I3L1B9
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.*105G>A		splice_region_variant, non_coding_transcript_exon_variant	4/5	4		ENSP00000477472.1	V9GZ69
ENSG00000285329	ENST00000575785.2 linkuse as main transcript	n.*105G>A		3_prime_UTR_variant	4/5	4		ENSP00000477472.1	V9GZ69

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000283

AC:

AN:

247456

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134326

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:

0.0000626

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1460572

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000723

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000617

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000495

AC:

EpiCase

AF:

0.000164

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 13, 2022

The c.109G>A (p.E37K) alteration is located in exon 3 (coding exon 1) of the NAA60 gene. This alteration results from a G to A substitution at nucleotide position 109, causing the glutamic acid (E) at amino acid position 37 to be replaced by a lysine (K). 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

0.97

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

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

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.;.;L;.;L;L;.;L;L;L;.;L;.;L;.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.8

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

REVEL

Uncertain

0.30

Sift

Benign

0.11

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

Sift4G

Benign

0.21

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

Polyphen

0.80

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

Vest4

0.81

MVP

0.093

MPC

0.45

ClinPred

0.54

GERP RS

5.6

Varity_R

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.70

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