12-112042102-C-A

Variant names:

• chr12-112042102-C-A
• rs1394962763
• NM_024953.4:c.2377G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25430745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA25	NM_024953.4	MANE Select	c.2377G>T	p.Asp793Tyr	missense splice_region	Exon 20 of 24	NP_079229.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA25	ENST00000261745.9	TSL:1 MANE Select	c.2377G>T	p.Asp793Tyr	missense splice_region	Exon 20 of 24	ENSP00000261745.4	Q14CX7-1
	NAA25	ENST00000549711.5	TSL:1	n.*2084G>T		splice_region non_coding_transcript_exon	Exon 20 of 24	ENSP00000448200.1	F8VSB9
	NAA25	ENST00000551858.1	TSL:1	n.*2464G>T		splice_region non_coding_transcript_exon	Exon 21 of 23	ENSP00000446719.1	F8W0N5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000669 AC: 1 AN: 149426 AF XY: 0.0000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000129

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000308 AC: 4 AN: 1298448 Hom.: 0 Cov.: 21 AF XY: 0.00000310 AC XY: 2 AN XY: 644902

African (AFR) AF: 0.00 AC: 0 AN: 25570

American (AMR) AF: 0.00 AC: 0 AN: 19708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21584

East Asian (EAS) AF: 0.00 AC: 0 AN: 32132

South Asian (SAS) AF: 0.00 AC: 0 AN: 65866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00000390 AC: 4 AN: 1025246

Other (OTH) AF: 0.00 AC: 0 AN: 53572

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.013	D
Polyphen		0.91	P
Vest4		0.41
MutPred		0.32		Loss of loop (P = 0.0235)
MVP		0.068
MPC		0.12
ClinPred		0.67	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.49
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1394962763; hg19: chr12-112479906;