16-3479490-C-T

Position:

• chr16-3479490-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001317095.2(NAA60):​c.-66C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000137 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAA60 NM_001317095.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.67

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-3479490-C-T is Pathogenic according to our data. Variant chr16-3479490-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 3076208.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.130C>T	p.Arg44Cys	missense_variant	4/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000360862.9	c.-66C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.-66C>T		5_prime_UTR_premature_start_codon_gain_variant	2/5	4		ENSP00000459055.1
NAA60	ENST00000407558.9	c.130C>T	p.Arg44Cys	missense_variant	4/8	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000424546.6	c.151C>T	p.Arg51Cys	missense_variant	3/7	2		ENSP00000401237.2
NAA60	ENST00000414063.6	c.130C>T	p.Arg44Cys	missense_variant	3/7	2		ENSP00000393224.2
NAA60	ENST00000360862.9	c.-66C>T		5_prime_UTR_variant	2/6	2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.-66C>T		5_prime_UTR_variant	2/5	4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.130C>T		non_coding_transcript_exon_variant	3/5	4		ENSP00000461438.1
ENSG00000285329	ENST00000575785.2	n.*126C>T		non_coding_transcript_exon_variant	5/5	4		ENSP00000477472.1
ENSG00000285329	ENST00000575785.2	n.*126C>T		3_prime_UTR_variant	5/5	4		ENSP00000477472.1
NAA60	ENST00000573345.5	n.111-3012C>T		intron_variant		4		ENSP00000458717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249014 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461640 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

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	Benign	0.14
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;.;.;T;T;.;T;T;T;.;T;T;T;.;T;T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D;D;.;D;.;.;D;D;.;.;D;.;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.;M;.;M;M;.;M;M;M;.;M;.;M;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D;.;.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;.;.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;.;D;D;.;D;D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;.;.;.;.;.;D;.;D;D;.;.;D;D;.;.;.;D;.;.
Vest4		0.59
MVP		0.043
MPC		0.80
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.70
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs748506439; hg19: chr16-3529490; COSMIC: COSV104675606; COSMIC: COSV104675606;