Genetic Variant NAA25:p.Leu915Ile (chr12-112033286-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024953.4(NAA25):c.2743C>A(p.Leu915Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,612,044 control chromosomes in the GnomAD database, including 7,437 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1944 hom., cov: 32)

Exomes 𝑓: 0.078 ( 5493 hom. )

Consequence

NAA25
NM_024953.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

Publications

26 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.001417309).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

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.2743C>A	p.Leu915Ile	missense	Exon 23 of 24	NP_079229.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAA25	ENST00000261745.9	TSL:1 MANE Select	c.2743C>A	p.Leu915Ile	missense	Exon 23 of 24	ENSP00000261745.4	Q14CX7-1
NAA25	ENST00000549711.5	TSL:1	n.*2450C>A		non_coding_transcript_exon	Exon 23 of 24	ENSP00000448200.1	F8VSB9
NAA25	ENST00000549711.5	TSL:1	n.*2450C>A		3_prime_UTR	Exon 23 of 24	ENSP00000448200.1	F8VSB9

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19585

AN:

152068

Hom.:

1929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0950

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0785

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.0759

AC:

18991

AN:

250334

AF XY:

0.0719

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.0643

Gnomad ASJ exome

AF:

0.0637

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0768

GnomAD4 exome

AF:

0.0777

AC:

113412

AN:

1459858

Hom.:

5493

Cov.:

AF XY:

0.0756

AC XY:

54933

AN XY:

726284

show subpopulations

African (AFR)

AF:

0.283

AC:

9455

AN:

33366

American (AMR)

AF:

0.0671

AC:

2974

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.0646

AC:

1684

AN:

26088

East Asian (EAS)

AF:

0.000202

AC:

AN:

39640

South Asian (SAS)

AF:

0.0409

AC:

3515

AN:

85900

European-Finnish (FIN)

AF:

0.0354

AC:

1892

AN:

53374

Middle Eastern (MID)

AF:

0.137

AC:

786

AN:

5748

European-Non Finnish (NFE)

AF:

0.0793

AC:

88097

AN:

1111100

Other (OTH)

AF:

0.0829

AC:

5001

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

5015

10030

15046

20061

25076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3268

6536

9804

13072

16340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.129

AC:

19635

AN:

152186

Hom.:

1944

Cov.:

AF XY:

0.124

AC XY:

9204

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.279

AC:

11573

AN:

41500

American (AMR)

AF:

0.0948

AC:

1449

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5192

South Asian (SAS)

AF:

0.0410

AC:

198

AN:

4826

European-Finnish (FIN)

AF:

0.0403

AC:

427

AN:

10592

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0785

AC:

5336

AN:

68012

Other (OTH)

AF:

0.128

AC:

270

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

798

1596

2395

3193

3991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0940

Hom.:

3043

Bravo

AF:

0.141

TwinsUK

AF:

0.0763

AC:

283

ALSPAC

AF:

0.0848

AC:

327

ESP6500AA

AF:

0.257

AC:

1133

ESP6500EA

AF:

0.0731

AC:

629

ExAC

AF:

0.0811

AC:

9841

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

PhyloP100

3.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.62

REVEL

Benign

0.083

Sift

Benign

0.12

Sift4G

Benign

0.21

Polyphen

0.96

Vest4

0.048

MPC

0.064

ClinPred

0.018

GERP RS

5.0

Varity_R

0.16

gMVP

0.089

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over