16-3483453-A-C

Position:

• chr16-3483453-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PP3_Moderate PP5

The NM_001083601.3(NAA60):​c.428A>C​(p.Asn143Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA60 NM_001083601.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.82

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a mutagenesis_site Strongly reduced acetyltransferase activity. (size 0) in uniprot entity NAA60_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895
• PP5: Variant 16-3483453-A-C is Pathogenic according to our data. Variant chr16-3483453-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 3076210.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.428A>C	p.Asn143Thr	missense_variant	6/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.428A>C	p.Asn143Thr	missense_variant	6/8	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.449A>C	p.Asn150Thr	missense_variant	5/7	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.428A>C	p.Asn143Thr	missense_variant	5/7	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.233A>C	p.Asn78Thr	missense_variant	4/6	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.233A>C	p.Asn78Thr	missense_variant	4/5	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.*67A>C		non_coding_transcript_exon_variant	4/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.*172A>C		non_coding_transcript_exon_variant	4/5	4		ENSP00000458717.1
NAA60	ENST00000572739.5	n.*67A>C		3_prime_UTR_variant	4/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.*172A>C		3_prime_UTR_variant	4/5	4		ENSP00000458717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249174 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135198

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Basal ganglia calcification, idiopathic, 9, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.;D;.;D;D;.;.;D;D;D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;.;.;.;.;.;D;.;.;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.5	M;.;M;.;M;M;.;.;M;M;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.2	D;D;.;.;.;.;D;.;D;.;.
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D;.;.;.;.;D;.;D;.;.
Sift4G	Uncertain	0.0040	D;D;.;D;.;.;D;.;D;D;D
Polyphen		1.0	D;.;D;.;D;D;.;.;D;D;D
Vest4		0.94
MutPred		0.73		Gain of glycosylation at N143 (P = 0.0265);.;Gain of glycosylation at N143 (P = 0.0265);.;Gain of glycosylation at N143 (P = 0.0265);Gain of glycosylation at N143 (P = 0.0265);.;.;Gain of glycosylation at N143 (P = 0.0265);Gain of glycosylation at N143 (P = 0.0265);Gain of glycosylation at N143 (P = 0.0265);
MVP		0.20
MPC		1.1
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.82

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: rs767025617; hg19: chr16-3533453;