12-112048335-G-T

Variant names:

• chr12-112048335-G-T
• rs760779525
• NM_024953.4:c.1837C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024953.4(NAA25):​c.1837C>A​(p.Arg613Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NAA25 NM_024953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• Publications: 0 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]

LOC124903022 (HGNC:):

ACMG classification

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, 0.853

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.1837C>A	p.Arg613Ser	missense	Exon 16 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.1837C>A	p.Arg613Ser	missense	Exon 16 of 24	ENSP00000261745.4	Q14CX7-1
	NAA25	ENST00000549711.5	TSL:1	n.*1544C>A		non_coding_transcript_exon	Exon 16 of 24	ENSP00000448200.1	F8VSB9
	NAA25	ENST00000551858.1	TSL:1	n.*1924C>A		non_coding_transcript_exon	Exon 17 of 23	ENSP00000446719.1	F8W0N5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0081	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		9.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.15	N
REVEL	Uncertain	0.37
Sift	Benign	0.83	T
Sift4G	Benign	0.13	T
Polyphen		0.46	P
Vest4		0.88
MutPred		0.80		Loss of MoRF binding (P = 0.0912)
MVP		0.63
MPC		1.8
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.82
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs760779525; hg19: chr12-112486139; COSMIC: COSV99927169;