16-3483416-C-T

Position:

chr16-3483416-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001083601.3(NAA60):c.391C>T(p.His131Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NAA60
NM_001083601.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.46

Variant links:

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 links:

NAA60 (HGNC:):

NAA60 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-3483416-C-T is Pathogenic according to our data. Variant chr16-3483416-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 3076207.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.17473766). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3 linkuse as main transcript	c.391C>T	p.His131Tyr	missense_variant	6/8	ENST00000407558.9	NP_001077070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAA60	ENST00000407558.9 linkuse as main transcript	c.391C>T	p.His131Tyr	missense_variant	6/8	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000424546.6 linkuse as main transcript	c.412C>T	p.His138Tyr	missense_variant	5/7	2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000414063.6 linkuse as main transcript	c.391C>T	p.His131Tyr	missense_variant	5/7	2		ENSP00000393224.2	Q9H7X0-1
NAA60	ENST00000360862.9 linkuse as main transcript	c.196C>T	p.His66Tyr	missense_variant	4/6	2		ENSP00000354108.5	Q9H7X0-3
NAA60	ENST00000573580.5 linkuse as main transcript	c.196C>T	p.His66Tyr	missense_variant	4/5	4		ENSP00000459055.1	Q9H7X0-3
NAA60	ENST00000572739.5 linkuse as main transcript	n.*30C>T		non_coding_transcript_exon_variant	4/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.*135C>T		non_coding_transcript_exon_variant	4/5	4		ENSP00000458717.1	I3L1B9
NAA60	ENST00000572739.5 linkuse as main transcript	n.*30C>T		3_prime_UTR_variant	4/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.*135C>T		3_prime_UTR_variant	4/5	4		ENSP00000458717.1	I3L1B9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248912

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135082

show subpopulations

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:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727080

show subpopulations

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:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

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

0.19

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.023

T;.;.;T;.;T;T;.;.;T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;D;.;.;.;.;.;D;.;.;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.68

N;.;.;N;.;N;N;.;.;N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.87

N;.;N;.;.;.;.;N;.;N;.;.

REVEL

Benign

0.20

Sift

Benign

1.0

T;.;T;.;.;.;.;T;.;T;.;.

Sift4G

Benign

1.0

T;T;T;.;T;.;.;T;.;T;T;T

Polyphen

0.035

B;.;.;B;.;B;B;.;.;B;B;B

Vest4

0.84

MutPred

0.26

Loss of disorder (P = 0.0341);Loss of disorder (P = 0.0341);.;Loss of disorder (P = 0.0341);.;Loss of disorder (P = 0.0341);Loss of disorder (P = 0.0341);.;.;Loss of disorder (P = 0.0341);Loss of disorder (P = 0.0341);Loss of disorder (P = 0.0341);

MVP

0.043

MPC

0.40

ClinPred

0.18

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over