chr14-57391666-G-A

Position:

• chr14-57391666-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001011713.3(NAA30):​c.709G>A​(p.Glu237Lys) 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: 33)
• Consequence: NAA30 NM_001011713.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54

Genes affected

NAA30 (HGNC:19844): (N-alpha-acetyltransferase 30, NatC catalytic subunit) Enables peptide alpha-N-acetyltransferase activity. Involved in N-terminal peptidyl-methionine acetylation. Located in cytosol and nucleus. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA30	NM_001011713.3	c.709G>A	p.Glu237Lys	missense_variant	2/5	ENST00000556492.6	NP_001011713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA30	ENST00000556492.6	c.709G>A	p.Glu237Lys	missense_variant	2/5	1	NM_001011713.3	ENSP00000452521.1
NAA30	ENST00000298406.6	c.204+160G>A		intron_variant		1		ENSP00000298406.6
NAA30	ENST00000554703.1	c.-4+961G>A		intron_variant		1		ENSP00000451255.1
NAA30	ENST00000555166.5	c.-4+961G>A		intron_variant		2		ENSP00000450939.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.709G>A (p.E237K) alteration is located in exon 2 (coding exon 1) of the NAA30 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the glutamic acid (E) at amino acid position 237 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.59		Gain of catalytic residue at E237 (P = 0.0028);
MVP		0.70
MPC		2.8
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.98

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: chr14-57858384;