rs12448488

Variant names:

• chr16-3456775-G-A
• rs12448488
• NM_001083601.3:c.-7+8235G>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+8235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,902 control chromosomes in the GnomAD database, including 4,946 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 0.23 (4946 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: NAA60 NM_001083601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083601.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA60	NM_001083601.3	MANE Select	c.-7+8235G>A		intron	N/A	NP_001077070.1	Q9H7X0-1
	NAA60	NM_001317093.1		c.131+8235G>A		intron	N/A	NP_001304022.1	Q9H7X0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA60	ENST00000407558.9	TSL:1 MANE Select	c.-7+8235G>A		intron	N/A	ENSP00000385903.4	Q9H7X0-1
	NAA60	ENST00000424546.6	TSL:2	c.131+8235G>A		intron	N/A	ENSP00000401237.2	Q9H7X0-2
	NAA60	ENST00000573580.5	TSL:4	c.-86+12948G>A		intron	N/A	ENSP00000459055.1	Q9H7X0-3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34161 AN: 151730 Hom.: 4921 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.148 AC: 8 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 8 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.114 AC: 5 AN: 44

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.226 AC: 34249 AN: 151848 Hom.: 4946 Cov.: 32 AF XY: 0.225 AC XY: 16679 AN XY: 74222

African (AFR) AF: 0.408 AC: 16867 AN: 41360

American (AMR) AF: 0.218 AC: 3320 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1251 AN: 5144

South Asian (SAS) AF: 0.240 AC: 1154 AN: 4810

European-Finnish (FIN) AF: 0.127 AC: 1339 AN: 10538

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9067 AN: 67966

Other (OTH) AF: 0.224 AC: 472 AN: 2104

Alfa AF: 0.173 Hom.: 3032

Bravo AF: 0.243

Asia WGS AF: 0.312 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.67
PhyloP100		-0.51
PromoterAI		0.0035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12448488; hg19: chr16-3506775;