chr16-3459056-G-A

Variant names:

• chr16-3459056-G-A
• rs40363
• NM_001083601.3:c.-7+10516G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083601.3(NAA60):​c.-7+10516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,124 control chromosomes in the GnomAD database, including 2,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2864 hom., cov: 32)
• Consequence: NAA60 NM_001083601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 9, autosomal recessive

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000285329 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.-7+10516G>A		intron_variant	Intron 2 of 7	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.-7+10516G>A		intron_variant	Intron 2 of 7	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.131+10516G>A		intron_variant	Intron 2 of 6	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.-7+875G>A		intron_variant	Intron 1 of 6	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.-86+875G>A		intron_variant	Intron 1 of 5	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.-86+15229G>A		intron_variant	Intron 1 of 4	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.-7+875G>A		intron_variant	Intron 1 of 4	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.-7+875G>A		intron_variant	Intron 1 of 4	4		ENSP00000458717.1
ENSG00000285329	ENST00000575785.2	n.281+10516G>A		intron_variant	Intron 3 of 4	4		ENSP00000477472.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29535 AN: 152006 Hom.: 2860 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29555 AN: 152124 Hom.: 2864 Cov.: 32 AF XY: 0.192 AC XY: 14311 AN XY: 74348

African (AFR) AF: 0.211 AC: 8755 AN: 41472

American (AMR) AF: 0.164 AC: 2509 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 585 AN: 3472

East Asian (EAS) AF: 0.156 AC: 807 AN: 5180

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4818

European-Finnish (FIN) AF: 0.186 AC: 1972 AN: 10584

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13123 AN: 68010

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.191 Hom.: 10837

Bravo AF: 0.192

Asia WGS AF: 0.197 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.063
DANN	Benign	0.75
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs40363; hg19: chr16-3509056;