rs12448488

Positions:

• chr16-3456775-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000285329 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.-7+8235G>A		intron_variant		ENST00000407558.9	NP_001077070.1
NAA60	NM_001317093.1	c.131+8235G>A		intron_variant			NP_001304022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.-7+8235G>A		intron_variant		1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.131+8235G>A		intron_variant		2		ENSP00000401237.2
NAA60	ENST00000573580.5	c.-86+12948G>A		intron_variant		4		ENSP00000459055.1
ENSG00000285329	ENST00000575785.2	n.281+8235G>A		intron_variant		4		ENSP00000477472.1

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

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.333

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

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.224

Alfa AF: 0.162 Hom.: 2031

Bravo AF: 0.243

Asia WGS AF: 0.312 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs12448488; hg19: chr16-3506775;