dbSNP rs1553996072: NAA15:p.Lys305Gln (chr4-139351510-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_057175.5(NAA15):c.913A>C(p.Lys305Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,423,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

NAA15
NM_057175.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.93

Publications

0 publications found

Variant links:

Genes affected

NAA15 (HGNC:30782): (N-alpha-acetyltransferase 15, NatA auxiliary subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex. [provided by RefSeq, Jan 2017]

NAA15 Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 50
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

NAA15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA15	NM_057175.5 link	c.913A>C	p.Lys305Gln	missense_variant	Exon 9 of 20	ENST00000296543.10	NP_476516.1
NAA15	NM_001410842.1 link	c.913A>C	p.Lys305Gln	missense_variant	Exon 9 of 20		NP_001397771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA15	ENST00000296543.10 link	c.913A>C	p.Lys305Gln	missense_variant	Exon 9 of 20	1	NM_057175.5	ENSP00000296543.4		Q9BXJ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1423298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32638

American (AMR)

AF:

0.00

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25790

East Asian (EAS)

AF:

0.00

AC:

AN:

39458

South Asian (SAS)

AF:

0.00

AC:

AN:

84664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078500

Other (OTH)

AF:

0.00

AC:

AN:

59008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

6.9

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.093

Sift

Benign

0.19

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.069

B;.

Vest4

0.28

MutPred

0.39

Loss of ubiquitination at K305 (P = 0.0381);Loss of ubiquitination at K305 (P = 0.0381);

MVP

0.40

MPC

0.60

ClinPred

0.76

GERP RS

6.1

Varity_R

0.34

gMVP

0.43

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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