dbSNP rs17696736: NAA25:c.1729-571T>C (chr12-112049014-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_024953.4(NAA25):c.1729-571T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.295 (AC=44,874) in the gnomAD database across 152,082 control chromosomes, including 9,161 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.434. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 9161 hom., cov: 32)

Consequence

NAA25
NM_024953.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

164 publications found

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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new If you want to explore the variant's impact on the transcript NM_024953.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4340 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA25	NM_024953.4	MANE Select	c.1729-571T>C		intron	N/A	NP_079229.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAA25	ENST00000261745.9	TSL:1 MANE Select	c.1729-571T>C	intron	N/A	ENSP00000261745.4	Q14CX7-1
NAA25	ENST00000549711.5	TSL:1	n.*1435+469T>C	intron	N/A	ENSP00000448200.1	F8VSB9
NAA25	ENST00000551858.1	TSL:1	n.*1816-571T>C	intron	N/A	ENSP00000446719.1	F8W0N5

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	0.295	44893	9165	151964	32
GnomAD4 genome	0.295	44874	9161	152082	32
TOPMed (Bravo)	0.281
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.389	292508	63747	752032
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.327	765	142	2342
ChinaMAP Phase 1	0.00276
Denmark Genome	0.517	155		300
GenomeAsia100K	0.0550	191		3478
Qatari Genome	0.171	30		176
ToMMo 61KJPN (+60KJPN MNV)	0.000383	47	6	122576
Turkish Variome	0.390	603	129	1546
UK10K	0.418	3160		7562
WBBC (Westlake BioBank for Chinese) pilot	0.000558	5	0	8960

Showing 13 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Uncertain	-	15
BayesDel_noAF	Benign	-	-0.78
CADD	Benign	-	16
DANN	Benign	-	0.55
GPN-Star LLR	N/A	-	-3.6
GPN-Star score	N/A	-	3.6
Mutation Taster	N/A	polymorphism (auto)	100/0
PhyloP100	Benign	-	0.085

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over