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).

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+10516G>T		intron	N/A	NP_001077070.1	Q9H7X0-1
	NAA60	NM_001317093.1		c.131+10516G>T		intron	N/A	NP_001304022.1	Q9H7X0-2
	NAA60	NM_001083600.3		c.-7+875G>T		intron	N/A	NP_001077069.1	Q9H7X0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA60	ENST00000407558.9	TSL:1 MANE Select	c.-7+10516G>T		intron	N/A	ENSP00000385903.4	Q9H7X0-1
	NAA60	ENST00000424546.6	TSL:2	c.131+10516G>T		intron	N/A	ENSP00000401237.2	Q9H7X0-2
	NAA60	ENST00000414063.6	TSL:2	c.-7+875G>T		intron	N/A	ENSP00000393224.2	Q9H7X0-1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs40363;

hg19: chr16-3509056;