4-139334229-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_057175.5(NAA15):​c.110T>C​(p.Leu37Pro) 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. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NAA15
NM_057175.5 missense

Scores

16
2
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
Variant links:
Genes affected
NAA15 (HGNC:30782): (N-alpha-acetyltransferase 15, NatA auxiliary subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex. [provided by RefSeq, Jan 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAA15NM_057175.5 linkuse as main transcriptc.110T>C p.Leu37Pro missense_variant 2/20 ENST00000296543.10 NP_476516.1
NAA15NM_001410842.1 linkuse as main transcriptc.110T>C p.Leu37Pro missense_variant 2/20 NP_001397771.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAA15ENST00000296543.10 linkuse as main transcriptc.110T>C p.Leu37Pro missense_variant 2/201 NM_057175.5 ENSP00000296543.4 Q9BXJ9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJan 31, 2024Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.33
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.61
D;.
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
0.44
D
MutationAssessor
Pathogenic
3.9
H;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Pathogenic
-6.5
D;D
REVEL
Pathogenic
0.85
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.98
MutPred
0.74
Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP
0.90
MPC
3.7
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.96
gMVP
0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-140255383; API