16-3484780-C-G

Position:

chr16-3484780-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001083601.3(NAA60):c.654C>G(p.His218Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,587,886 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

NAA60
NM_001083601.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.56

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024121106).

BP6

Variant 16-3484780-C-G is Benign according to our data. Variant chr16-3484780-C-G is described in ClinVar as [Benign]. Clinvar id is 780018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1892/152382) while in subpopulation AFR AF= 0.0432 (1795/41592). AF 95% confidence interval is 0.0415. There are 39 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA60	NM_001083601.3 linkuse as main transcript	c.654C>G	p.His218Gln	missense_variant	7/8	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.654C>G	p.His218Gln	missense_variant	7/8	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000424546.6 linkuse as main transcript	c.675C>G	p.His225Gln	missense_variant	6/7	2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000414063.6 linkuse as main transcript	c.654C>G	p.His218Gln	missense_variant	6/7	2		ENSP00000393224.2	Q9H7X0-1
NAA60	ENST00000360862.9 linkuse as main transcript	c.459C>G	p.His153Gln	missense_variant	5/6	2		ENSP00000354108.5	Q9H7X0-3
NAA60	ENST00000573580.5 linkuse as main transcript	c.459C>G	p.His153Gln	missense_variant	5/5	4		ENSP00000459055.1	Q9H7X0-3
NAA60	ENST00000572739.5 linkuse as main transcript	n.*293C>G		non_coding_transcript_exon_variant	5/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000572739.5 linkuse as main transcript	n.*293C>G		3_prime_UTR_variant	5/5	4		ENSP00000461438.1	I3L4Q3
NAA60	ENST00000573345.5 linkuse as main transcript	n.*398C>G		downstream_gene_variant		4		ENSP00000458717.1	I3L1B9

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1875

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00304

AC:

623

AN:

204852

Hom.:

AF XY:

0.00225

AC XY:

249

AN XY:

110790

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.00187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000777

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00135

AC:

1942

AN:

1435504

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

834

AN XY:

711756

show subpopulations

Gnomad4 AFR exome

AF:

0.0477

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000146

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000600

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.0124

AC:

1892

AN:

152382

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

868

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.0142

ESP6500AA

AF:

0.0424

AC:

176

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.00333

AC:

401

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 04, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.015

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

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

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

MetaRNN

Benign

0.0024

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

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.74

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

REVEL

Benign

0.15

Sift

Benign

0.87

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

Sift4G

Benign

0.57

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

Polyphen

0.0

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

Vest4

0.070

MutPred

0.11

Loss of catalytic residue at L220 (P = 0.1827);.;Loss of catalytic residue at L220 (P = 0.1827);.;Loss of catalytic residue at L220 (P = 0.1827);Loss of catalytic residue at L220 (P = 0.1827);.;.;Loss of catalytic residue at L220 (P = 0.1827);Loss of catalytic residue at L220 (P = 0.1827);.;Loss of catalytic residue at L220 (P = 0.1827);

MVP

0.043

MPC

0.33

ClinPred

0.0043

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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