Variant 12-112042102-C-A 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.2377G>T(p.Asp793Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000308 in 1,298,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

NAA25
NM_024953.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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:

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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=0.25430745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA25	NM_024953.4 link	c.2377G>T	p.Asp793Tyr	missense_variant, splice_region_variant	20/24	ENST00000261745.9	NP_079229.2	Q14CX7-1
NAA25	XM_006719606.3 link	c.2293G>T	p.Asp765Tyr	missense_variant, splice_region_variant	20/24		XP_006719669.1
NAA25	XM_047429557.1 link	c.1969G>T	p.Asp657Tyr	missense_variant, splice_region_variant	17/21		XP_047285513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA25	ENST00000261745.9 link	c.2377G>T	p.Asp793Tyr	missense_variant, splice_region_variant	20/24	1	NM_024953.4	ENSP00000261745.4		Q14CX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000308

AC:

AN:

1298448

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

644902

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:

0.00000390

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

Jan 03, 2024

The c.2377G>T (p.D793Y) alteration is located in exon 20 (coding exon 20) of the NAA25 gene. This alteration results from a G to T substitution at nucleotide position 2377, causing the aspartic acid (D) at amino acid position 793 to be replaced by a tyrosine (Y). 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

Benign

0.12

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0083

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Uncertain

0.010

Sift4G

Uncertain

0.013

Polyphen

0.91

Vest4

0.41

MutPred

0.32

Loss of loop (P = 0.0235);

MVP

0.068

MPC

0.12

ClinPred

0.67

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.49

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

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