rs28810

chr16-3450515-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NAA60	NM_001083601.3	c.-7+1975A>G		intron_variant		ENST00000407558.9
NAA60	NM_001317093.1	c.131+1975A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA60	ENST00000407558.9	c.-7+1975A>G		intron_variant		1	NM_001083601.3	P1

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

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.152

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

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

LitVar

Other links and lift over

dbSNP: rs28810; hg19: chr16-3500515;