rs40363

Positions:

• chr16-3459056-G-A
• chr16-3459056-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.-7+10516G>A		intron_variant		ENST00000407558.9	NP_001077070.1

Ensembl

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.189

Alfa AF: 0.187 Hom.: 4323

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

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: rs40363; hg19: chr16-3509056;