16-3484706-A-C

Position:

• chr16-3484706-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083601.3(NAA60):​c.580A>C​(p.Ile194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,439,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NAA60 NM_001083601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16198978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.580A>C	p.Ile194Leu	missense_variant	7/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.580A>C	p.Ile194Leu	missense_variant	7/8	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.601A>C	p.Ile201Leu	missense_variant	6/7	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.580A>C	p.Ile194Leu	missense_variant	6/7	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.385A>C	p.Ile129Leu	missense_variant	5/6	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.385A>C	p.Ile129Leu	missense_variant	5/5	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.*219A>C		non_coding_transcript_exon_variant	5/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.*324A>C		non_coding_transcript_exon_variant	5/5	4		ENSP00000458717.1
NAA60	ENST00000572739.5	n.*219A>C		3_prime_UTR_variant	5/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.*324A>C		3_prime_UTR_variant	5/5	4		ENSP00000458717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1439648 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 714268

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: 0.00000181

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

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

Jun 05, 2024

The c.580A>C (p.I194L) alteration is located in exon 7 (coding exon 5) of the NAA60 gene. This alteration results from a A to C substitution at nucleotide position 580, causing the isoleucine (I) at amino acid position 194 to be replaced by a leucine (L). 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	0.066
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.97
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.88	T
PROVEAN	Benign	-0.66	N
REVEL	Uncertain	0.30
Sift	Benign	0.086	T
Sift4G	Benign	0.066	T
Vest4		0.29
MutPred		0.49		Gain of glycosylation at H118 (P = 0.0166);
MVP		0.068
ClinPred		0.87	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3534706;