rs28810

Variant names:

• chr16-3450515-A-G
• rs28810
• NM_001083601.3:c.-7+1975A>G

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+1975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,930 control chromosomes in the GnomAD database, including 2,417 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 0.16 (2417 hom., cov: 30)
• Consequence: NAA60 NM_001083601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.-7+1975A>G		intron_variant	Intron 2 of 7	ENST00000407558.9	NP_001077070.1
NAA60	NM_001317093.1	c.131+1975A>G		intron_variant	Intron 2 of 6		NP_001304022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.-7+1975A>G		intron_variant	Intron 2 of 7	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.131+1975A>G		intron_variant	Intron 2 of 6	2		ENSP00000401237.2
NAA60	ENST00000573580.5	c.-86+6688A>G		intron_variant	Intron 1 of 4	4		ENSP00000459055.1
ENSG00000285329	ENST00000575785.2	n.281+1975A>G		intron_variant	Intron 3 of 4	4		ENSP00000477472.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24025 AN: 151812 Hom.: 2416 Cov.: 30

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.158 AC: 24023 AN: 151930 Hom.: 2417 Cov.: 30 AF XY: 0.155 AC XY: 11514 AN XY: 74242

African (AFR) AF: 0.0425 AC: 1765 AN: 41512

American (AMR) AF: 0.177 AC: 2702 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3466

East Asian (EAS) AF: 0.0403 AC: 208 AN: 5158

South Asian (SAS) AF: 0.104 AC: 501 AN: 4816

European-Finnish (FIN) AF: 0.213 AC: 2240 AN: 10526

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15330 AN: 67896

Other (OTH) AF: 0.152 AC: 318 AN: 2096

Alfa AF: 0.185 Hom.: 380

Bravo AF: 0.152

Asia WGS AF: 0.0810 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		-0.32
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: rs28810; hg19: chr16-3500515;