14-57391249-G-C

Position:

• chr14-57391249-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001011713.3(NAA30):​c.292G>C​(p.Ala98Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.21

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA30	NM_001011713.3	c.292G>C	p.Ala98Pro	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.292G>C	p.Ala98Pro	missense_variant	2/5	1	NM_001011713.3	ENSP00000452521.1
NAA30	ENST00000554703.1	c.-4+544G>C		intron_variant		1		ENSP00000451255.1
NAA30	ENST00000555166.5	c.-4+544G>C		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

Jun 30, 2022

The c.292G>C (p.A98P) alteration is located in exon 2 (coding exon 1) of the NAA30 gene. This alteration results from a G to C substitution at nucleotide position 292, causing the alanine (A) at amino acid position 98 to be replaced by a proline (P). 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	Benign	0.22
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.20	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.41		Loss of helix (P = 0.0072);
MVP		0.47
MPC		0.59
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.69
gMVP		0.23

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: chr14-57857967;