11-63952263-C-G

Variant names:

• chr11-63952263-C-G
• NM_024771.4:c.181C>G

Variant summary

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

The NM_024771.4(NAA40):​c.181C>G​(p.Arg61Gly) variant causes a missense change involving the alteration of a non-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: 1.33

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.181C>G	p.Arg61Gly	missense_variant	Exon 4 of 8	ENST00000377793.9	NP_079047.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA40	ENST00000377793.9	c.181C>G	p.Arg61Gly	missense_variant	Exon 4 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

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.181C>G (p.R61G) alteration is located in exon 4 (coding exon 4) of the NAA40 gene. This alteration results from a C to G substitution at nucleotide position 181, causing the arginine (R) at amino acid position 61 to be replaced by a glycine (G). 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	0.68
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.084	T;D
Polyphen		0.80	P;.
Vest4		0.88
MutPred		0.45		Gain of catalytic residue at R61 (P = 0.0424);.;
MVP		0.61
MPC		0.99
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.71
gMVP		0.89

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: chr11-63719735; COSMIC: COSV100624231; COSMIC: COSV100624231;