16-3459056-G-T

Variant names:

• chr16-3459056-G-T
• rs40363
• NM_001083601.3:c.-7+10516G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083601.3(NAA60):​c.-7+10516G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NAA60 NM_001083601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.-7+10516G>T		intron_variant	Intron 2 of 7	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.-7+10516G>T		intron_variant	Intron 2 of 7	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.131+10516G>T		intron_variant	Intron 2 of 6	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.-7+875G>T		intron_variant	Intron 1 of 6	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.-86+875G>T		intron_variant	Intron 1 of 5	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.-86+15229G>T		intron_variant	Intron 1 of 4	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.-7+875G>T		intron_variant	Intron 1 of 4	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.-7+875G>T		intron_variant	Intron 1 of 4	4		ENSP00000458717.1
ENSG00000285329	ENST00000575785.2	n.281+10516G>T		intron_variant	Intron 3 of 4	4		ENSP00000477472.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.033
DANN	Benign	0.49
PhyloP100		-0.87

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: rs40363; hg19: chr16-3509056;