rs201680695

Variant names:

• chr11-63952522-C-T
• rs201680695
• NM_024771.4:c.367C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_024771.4(NAA40):​c.367C>T​(p.His123Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: NAA40 NM_024771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA40	NM_024771.4	MANE Select	c.367C>T	p.His123Tyr	missense	Exon 5 of 8	NP_079047.2	Q86UY6-1
	NAA40	NM_001300800.1		c.304C>T	p.His102Tyr	missense	Exon 5 of 8	NP_001287729.1	Q86UY6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA40	ENST00000377793.9	TSL:1 MANE Select	c.367C>T	p.His123Tyr	missense	Exon 5 of 8	ENSP00000367024.4	Q86UY6-1
	NAA40	ENST00000338447.10	TSL:1	n.1520C>T		non_coding_transcript_exon	Exon 4 of 7
	NAA40	ENST00000954956.1		c.631C>T	p.His211Tyr	missense	Exon 6 of 9	ENSP00000625015.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000211 AC: 53 AN: 251480 AF XY: 0.000213

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000345 AC: 504 AN: 1461894 Hom.: 1 Cov.: 32 AF XY: 0.000352 AC XY: 256 AN XY: 727248

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000423 AC: 470 AN: 1112012

Other (OTH) AF: 0.000315 AC: 19 AN: 60396

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74340

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.000197 AC: 3 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000316 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.94
MVP		0.54
MPC		1.3
ClinPred		0.68	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.83
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201680695; hg19: chr11-63719994;