chr16-3483540-A-G

Position:

chr16-3483540-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001083601.3(NAA60):c.515A>G(p.Lys172Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NAA60
NM_001083601.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82

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:

NAA60 (HGNC:):

NAA60 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3542755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3 linkuse as main transcript	c.515A>G	p.Lys172Arg	missense_variant	6/8	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.515A>G	p.Lys172Arg	missense_variant	6/8	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000424546.6 linkuse as main transcript	c.536A>G	p.Lys179Arg	missense_variant	5/7	2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000414063.6 linkuse as main transcript	c.515A>G	p.Lys172Arg	missense_variant	5/7	2		ENSP00000393224.2	Q9H7X0-1
NAA60	ENST00000360862.9 linkuse as main transcript	c.320A>G	p.Lys107Arg	missense_variant	4/6	2		ENSP00000354108.5	Q9H7X0-3
NAA60	ENST00000573580.5 linkuse as main transcript	c.320A>G	p.Lys107Arg	missense_variant	4/5	4		ENSP00000459055.1	Q9H7X0-3
NAA60	ENST00000572739.5 linkuse as main transcript	n.*154A>G		non_coding_transcript_exon_variant	4/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.*259A>G		non_coding_transcript_exon_variant	4/5	4		ENSP00000458717.1	I3L1B9
NAA60	ENST00000572739.5 linkuse as main transcript	n.*154A>G		3_prime_UTR_variant	4/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.*259A>G		3_prime_UTR_variant	4/5	4		ENSP00000458717.1	I3L1B9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000402

AC:

AN:

248584

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461262

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000247

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000413

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 03, 2023

The c.515A>G (p.K172R) alteration is located in exon 6 (coding exon 4) of the NAA60 gene. This alteration results from a A to G substitution at nucleotide position 515, causing the lysine (K) at amino acid position 172 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

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

Eigen

Benign

0.072

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.016

MetaRNN

Benign

0.35

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

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

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.15

Sift

Benign

0.10

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

Sift4G

Benign

0.17

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

Polyphen

0.011

B;.;B;.;B;B;.;.;B;B;B

Vest4

0.62

MutPred

0.53

Loss of methylation at K172 (P = 0.0312);.;Loss of methylation at K172 (P = 0.0312);.;Loss of methylation at K172 (P = 0.0312);Loss of methylation at K172 (P = 0.0312);.;.;Loss of methylation at K172 (P = 0.0312);Loss of methylation at K172 (P = 0.0312);Loss of methylation at K172 (P = 0.0312);

MVP

0.043

MPC

0.28

ClinPred

0.15

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.54

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