chr12-112033286-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000261745.9(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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1944 hom., cov: 32)
Exomes 𝑓: 0.078 ( 5493 hom. )

Consequence

NAA25
ENST00000261745.9 missense

Scores

4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAA25NM_024953.4 linkuse as main transcriptc.2743C>A p.Leu915Ile missense_variant 23/24 ENST00000261745.9 NP_079229.2
NAA25XM_006719606.3 linkuse as main transcriptc.2659C>A p.Leu887Ile missense_variant 23/24 XP_006719669.1
NAA25XM_047429557.1 linkuse as main transcriptc.2335C>A p.Leu779Ile missense_variant 20/21 XP_047285513.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAA25ENST00000261745.9 linkuse as main transcriptc.2743C>A p.Leu915Ile missense_variant 23/241 NM_024953.4 ENSP00000261745 P1Q14CX7-1
NAA25ENST00000549711.5 linkuse as main transcriptc.*2450C>A 3_prime_UTR_variant, NMD_transcript_variant 23/241 ENSP00000448200
NAA25ENST00000548181.1 linkuse as main transcriptn.2120C>A non_coding_transcript_exon_variant 1/22
NAA25ENST00000552527.5 linkuse as main transcriptn.3896C>A non_coding_transcript_exon_variant 22/232

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19585
AN:
152068
Hom.:
1929
Cov.:
32
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
GnomAD3 exomes
AF:
0.0759
AC:
18991
AN:
250334
Hom.:
1218
AF XY:
0.0719
AC XY:
9738
AN XY:
135352
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 SAS exome
AF:
0.0413
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.:
31
AF XY:
0.0756
AC XY:
54933
AN XY:
726284
show subpopulations
Gnomad4 AFR exome
AF:
0.283
Gnomad4 AMR exome
AF:
0.0671
Gnomad4 ASJ exome
AF:
0.0646
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0409
Gnomad4 FIN exome
AF:
0.0354
Gnomad4 NFE exome
AF:
0.0793
Gnomad4 OTH exome
AF:
0.0829
GnomAD4 genome
AF:
0.129
AC:
19635
AN:
152186
Hom.:
1944
Cov.:
32
AF XY:
0.124
AC XY:
9204
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.279
Gnomad4 AMR
AF:
0.0948
Gnomad4 ASJ
AF:
0.0608
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0410
Gnomad4 FIN
AF:
0.0403
Gnomad4 NFE
AF:
0.0785
Gnomad4 OTH
AF:
0.128
Alfa
AF:
0.0834
Hom.:
1498
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 v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.018
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.81
T
MetaRNN
Benign
0.0014
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.023
P
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.62
N
REVEL
Benign
0.083
Sift
Benign
0.12
T
Sift4G
Benign
0.21
T
Polyphen
0.96
D
Vest4
0.048
MPC
0.064
ClinPred
0.018
T
GERP RS
5.0
Varity_R
0.16
gMVP
0.089

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.

Other links and lift over

dbSNP: rs12298022; hg19: chr12-112471090; COSMIC: COSV55704380; COSMIC: COSV55704380; API