16-3476277-T-G

Position:

• chr16-3476277-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001083601.3(NAA60):​c.50T>G​(p.Leu17Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NAA60 NM_001083601.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.50

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-3476277-T-G is Pathogenic according to our data. Variant chr16-3476277-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 3076209.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.27199024). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3	c.50T>G	p.Leu17Arg	missense_variant	3/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA60	ENST00000407558.9	c.50T>G	p.Leu17Arg	missense_variant	3/8	1	NM_001083601.3	ENSP00000385903.4
NAA60	ENST00000414063.6	c.50T>G	p.Leu17Arg	missense_variant	2/7	2		ENSP00000393224.2
NAA60	ENST00000424546.6	c.132-3194T>G		intron_variant		2		ENSP00000401237.2
NAA60	ENST00000360862.9	c.-85-3194T>G		intron_variant		2		ENSP00000354108.5
NAA60	ENST00000573580.5	c.-85-3194T>G		intron_variant		4		ENSP00000459055.1
NAA60	ENST00000572739.5	n.50T>G		non_coding_transcript_exon_variant	2/5	4		ENSP00000461438.1
NAA60	ENST00000573345.5	n.50T>G		non_coding_transcript_exon_variant	2/5	4		ENSP00000458717.1
ENSG00000285329	ENST00000575785.2	n.*46T>G		non_coding_transcript_exon_variant	4/5	4		ENSP00000477472.1
ENSG00000285329	ENST00000575785.2	n.*46T>G		3_prime_UTR_variant	4/5	4		ENSP00000477472.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249122 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135028

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455404 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 724030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.;T;.;T;T;.;T;T;T;.;T;T;T;.;T;T;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	0.078
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D;D;D;D;.;D;.;.;D;D;.;.;D;.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;.;.;N;.;N;N;.;N;N;N;.;N;.;N;.;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N;.;.;.;.;.;.;.;.;.;N;N;.;.;.;.;.;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.011	D;.;.;.;.;.;.;.;.;.;T;D;.;.;.;.;.;.;.
Sift4G	Benign	0.075	T;T;D;D;D;.;T;T;.;T;D;T;T;D;D;D;T;T;D
Polyphen		0.0090	B;.;.;.;.;B;.;B;B;.;.;B;B;.;.;.;B;.;.
Vest4		0.72
MutPred		0.41		Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);Loss of stability (P = 0.0209);
MVP		0.19
MPC		0.49
ClinPred		0.37	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82

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: rs756008307; hg19: chr16-3526277;