dbSNP rs12448488: NAA60:c.-7+8235G>A (chr16-3456775-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001083601.3(NAA60):c.-7+8235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,902 control chromosomes in the GnomAD database, including 4,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4946 hom., cov: 32)

Exomes 𝑓: 0.15 ( 0 hom. )

Consequence

NAA60
NM_001083601.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

basal ganglia calcification, idiopathic, 9, autosomal recessive
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

NAA60 links:

ENSG00000285329 (HGNC:):

ENSG00000285329 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA60	NM_001083601.3 link	c.-7+8235G>A		intron_variant	Intron 2 of 7	ENST00000407558.9	NP_001077070.1
NAA60	NM_001317093.1 link	c.131+8235G>A		intron_variant	Intron 2 of 6		NP_001304022.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAA60	ENST00000407558.9 link	c.-7+8235G>A	intron_variant	Intron 2 of 7	1	NM_001083601.3	ENSP00000385903.4	Q9H7X0-1
NAA60	ENST00000424546.6 link	c.131+8235G>A	intron_variant	Intron 2 of 6	2		ENSP00000401237.2	Q9H7X0-2
NAA60	ENST00000573580.5 link	c.-86+12948G>A	intron_variant	Intron 1 of 4	4		ENSP00000459055.1	Q9H7X0-3
ENSG00000285329	ENST00000575785.2 link	n.281+8235G>A	intron_variant	Intron 3 of 4	4		ENSP00000477472.1	V9GZ69

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34161

AN:

151730

Hom.:

4921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.148

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.114

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

34249

AN:

151848

Hom.:

4946

Cov.:

AF XY:

0.225

AC XY:

16679

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.408

AC:

16867

AN:

41360

American (AMR)

AF:

0.218

AC:

3320

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

616

AN:

3470

East Asian (EAS)

AF:

0.243

AC:

1251

AN:

5144

South Asian (SAS)

AF:

0.240

AC:

1154

AN:

4810

European-Finnish (FIN)

AF:

0.127

AC:

1339

AN:

10538

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9067

AN:

67966

Other (OTH)

AF:

0.224

AC:

472

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1240

2480

3720

4960

6200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

3032

Bravo

AF:

0.243

Asia WGS

AF:

0.312

AC:

1083

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.19

(source)

DANN

Benign

0.67

PhyloP100

-0.51

PromoterAI

0.0035

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over