dbSNP rs749535695: NAA16:p.Arg91Ser (chr13-41320693-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024561.5(NAA16):c.271C>A(p.Arg91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,458,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NAA16
NM_024561.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

Genes affected

NAA16 (HGNC:26164): (N-alpha-acetyltransferase 16, NatA auxiliary subunit) Enables ribosome binding activity. Involved in N-terminal protein amino acid acetylation; negative regulation of apoptotic process; and protein stabilization. Located in cytosol. Part of NatA complex. [provided by Alliance of Genome Resources, Apr 2022]

NAA16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA16	NM_024561.5 link	c.271C>A	p.Arg91Ser	missense_variant	Exon 4 of 20	ENST00000379406.8	NP_078837.3	Q6N069-1A4FU51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAA16	ENST00000379406.8 link	c.271C>A	p.Arg91Ser	missense_variant	Exon 4 of 20	1	NM_024561.5	ENSP00000368716.3	Q6N069-1
NAA16	ENST00000403412.7 link	c.271C>A	p.Arg91Ser	missense_variant	Exon 4 of 11	1		ENSP00000386103.3	Q6N069-4
NAA16	ENST00000476980.5 link	n.518C>A		non_coding_transcript_exon_variant	Exon 4 of 10	1
NAA16	ENST00000464857.5 link	n.271C>A		non_coding_transcript_exon_variant	Exon 4 of 15	2		ENSP00000432364.1	Q6N069-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458940

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4850

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111314

Other (OTH)

AF:

0.00

AC:

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.271C>A (p.R91S) alteration is located in exon 4 (coding exon 4) of the NAA16 gene. This alteration results from a C to A substitution at nucleotide position 271, causing the arginine (R) at amino acid position 91 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

0.25

MutationAssessor

Pathogenic

3.4

M;M

PhyloP100

1.7

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.82

MutPred

0.74

Gain of catalytic residue at Y86 (P = 0.0032);Gain of catalytic residue at Y86 (P = 0.0032);

MVP

0.81

MPC

0.40

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.73

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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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rs749535695

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over