chr16-3483377-G-A

Position:

• chr16-3483377-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001083601.3(NAA60):​c.352G>A​(p.Glu118Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA60 NM_001083601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.46

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 (HGNC:):

ACMG classification

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=0.3813491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.352G>A	p.Glu118Lys	missense_variant	6/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.352G>A	p.Glu118Lys	missense_variant	6/8	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.373G>A	p.Glu125Lys	missense_variant	5/7	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.352G>A	p.Glu118Lys	missense_variant	5/7	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.157G>A	p.Glu53Lys	missense_variant	4/6	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.157G>A	p.Glu53Lys	missense_variant	4/5	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.255G>A		non_coding_transcript_exon_variant	4/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.*96G>A		non_coding_transcript_exon_variant	4/5	4		ENSP00000458717.1
NAA60	ENST00000573345.5	n.*96G>A		3_prime_UTR_variant	4/5	4		ENSP00000458717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.352G>A (p.E118K) alteration is located in exon 6 (coding exon 4) of the NAA60 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the glutamic acid (E) at amino acid position 118 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	0.83
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;.;T;.;T;.;T;T;T;.;.;T;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	.;D;D;D;.;.;.;.;D;.;D;.;.;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.53	N;.;.;.;N;.;N;N;.;.;.;N;N;N;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N;.;.;N;.;.;.;.;.;N;.;N;.;.;.
REVEL	Benign	0.19
Sift	Uncertain	0.017	D;.;.;D;.;.;.;.;.;D;.;D;.;.;.
Sift4G	Benign	0.070	T;T;D;T;.;T;.;.;D;T;.;T;T;T;D
Polyphen		0.12	B;.;.;.;B;.;B;B;.;.;.;B;B;B;.
Vest4		0.53
MutPred		0.45		Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);.;Gain of MoRF binding (P = 0.0604);.;Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);.;.;Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);Gain of MoRF binding (P = 0.0604);
MVP		0.043
MPC		0.47
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.75
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3533377;