14-57396817-C-G

Position:

• chr14-57396817-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001011713.3(NAA30):​c.837C>G​(p.Phe279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 2.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3326969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA30	NM_001011713.3	c.837C>G	p.Phe279Leu	missense_variant	3/5	ENST00000556492.6	NP_001011713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA30	ENST00000556492.6	c.837C>G	p.Phe279Leu	missense_variant	3/5	1	NM_001011713.3	ENSP00000452521.1
NAA30	ENST00000298406.6	c.270C>G	p.Phe90Leu	missense_variant	2/4	1		ENSP00000298406.6
NAA30	ENST00000554703.1	c.63C>G	p.Phe21Leu	missense_variant	2/3	1		ENSP00000451255.1
NAA30	ENST00000555166.5	c.63C>G	p.Phe21Leu	missense_variant	2/4	2		ENSP00000450939.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Aug 10, 2021

The c.837C>G (p.F279L) alteration is located in exon 3 (coding exon 2) of the NAA30 gene. This alteration results from a C to G substitution at nucleotide position 837, causing the phenylalanine (F) at amino acid position 279 to be replaced by a leucine (L). 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	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	.;N;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.65	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.012	.;B;.
Vest4		0.59
MutPred		0.37		.;Gain of catalytic residue at Y283 (P = 0.0186);.;
MVP		0.33
MPC		1.7
ClinPred		0.85	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.97

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: chr14-57863535;