Variant 12-112047754-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024953.4(NAA25):c.1917C>G(p.Asn639Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAA25
NM_024953.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

NAA25 (HGNC:25783): (N-alpha-acetyltransferase 25, NatB auxiliary subunit) This gene encodes the auxiliary subunit of the heteromeric N-terminal acetyltransferase B complex. This complex acetylates methionine residues that are followed by acidic or asparagine residues.[provided by RefSeq, Mar 2010]

NAA25 links:

LOC124903022 (HGNC:):

LOC124903022 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15972316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA25	NM_024953.4 link	c.1917C>G	p.Asn639Lys	missense_variant	17/24	ENST00000261745.9	NP_079229.2	Q14CX7-1
NAA25	XM_006719606.3 link	c.1833C>G	p.Asn611Lys	missense_variant	17/24		XP_006719669.1
NAA25	XM_047429557.1 link	c.1509C>G	p.Asn503Lys	missense_variant	14/21		XP_047285513.1
LOC124903022	XR_007063465.1 link	n.1959+1143G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA25	ENST00000261745.9 link	c.1917C>G	p.Asn639Lys	missense_variant	17/24	1	NM_024953.4	ENSP00000261745.4		Q14CX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461242

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726898

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.1917C>G (p.N639K) alteration is located in exon 17 (coding exon 17) of the NAA25 gene. This alteration results from a C to G substitution at nucleotide position 1917, causing the asparagine (N) at amino acid position 639 to be replaced by a lysine (K). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.010

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.99

REVEL

Benign

0.074

Sift

Benign

0.18

Sift4G

Benign

0.29

Polyphen

0.028

Vest4

0.20

MutPred

0.49

Gain of ubiquitination at N639 (P = 0.0094);

MVP

0.12

MPC

1.0

ClinPred

0.36

GERP RS

0.71

Varity_R

0.10

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over