11-63945927-G-C

Variant names:

• chr11-63945927-G-C
• NM_024771.4:c.94G>C

Variant summary

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

The NM_024771.4(NAA40):​c.94G>C​(p.Ala32Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAA40 NM_024771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

Genes affected

NAA40 (HGNC:25845): (N-alpha-acetyltransferase 40, NatD catalytic subunit) Enables H2A histone acetyltransferase activity; H4 histone acetyltransferase activity; and peptide-serine-N-acetyltransferase activity. Involved in N-terminal protein amino acid acetylation; histone H2A acetylation; and histone H4 acetylation. Located in centriolar satellite; cytosol; and nucleoplasm. [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 rank	MANE	Protein	UniProt
NAA40	NM_024771.4	c.94G>C	p.Ala32Pro	missense_variant	Exon 2 of 8	ENST00000377793.9	NP_079047.2
NAA40	NM_001300800.1	c.31G>C	p.Ala11Pro	missense_variant	Exon 2 of 8		NP_001287729.1
NAA40	XM_006718689.4	c.94G>C	p.Ala32Pro	missense_variant	Exon 2 of 8		XP_006718752.1
NAA40	XM_011545254.3	c.-83G>C		5_prime_UTR_variant	Exon 2 of 9		XP_011543556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA40	ENST00000377793.9	c.94G>C	p.Ala32Pro	missense_variant	Exon 2 of 8	1	NM_024771.4	ENSP00000367024.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94G>C (p.A32P) alteration is located in exon 2 (coding exon 2) of the NAA40 gene. This alteration results from a G to C substitution at nucleotide position 94, causing the alanine (A) at amino acid position 32 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	0.094	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.7	D;N;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.88
MutPred		0.50		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);.;
MVP		0.83
MPC		1.3
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.95
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-63713399;