11-63941102-C-T

Variant names:

• chr11-63941102-C-T
• rs728919
• NM_024771.4:c.6+2000C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024771.4(NAA40):​c.6+2000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,088 control chromosomes in the GnomAD database, including 21,924 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21924 hom., cov: 33)
• Consequence: NAA40 NM_024771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA40	NM_024771.4	c.6+2000C>T		intron_variant	Intron 1 of 7	ENST00000377793.9	NP_079047.2
NAA40	NM_001300800.1	c.-58+1568C>T		intron_variant	Intron 1 of 7		NP_001287729.1
NAA40	XM_006718689.4	c.6+2000C>T		intron_variant	Intron 1 of 7		XP_006718752.1
NAA40	XM_011545254.3	c.-171+2000C>T		intron_variant	Intron 1 of 8		XP_011543556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA40	ENST00000377793.9	c.6+2000C>T		intron_variant	Intron 1 of 7	1	NM_024771.4	ENSP00000367024.4

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78736 AN: 151970 Hom.: 21917 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78760 AN: 152088 Hom.: 21924 Cov.: 33 AF XY: 0.525 AC XY: 39072 AN XY: 74352

African (AFR) AF: 0.313 AC: 12977 AN: 41472

American (AMR) AF: 0.687 AC: 10502 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3466

East Asian (EAS) AF: 0.866 AC: 4495 AN: 5188

South Asian (SAS) AF: 0.594 AC: 2869 AN: 4832

European-Finnish (FIN) AF: 0.571 AC: 6030 AN: 10562

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38345 AN: 67972

Other (OTH) AF: 0.560 AC: 1182 AN: 2112

Alfa AF: 0.557 Hom.: 27506

Bravo AF: 0.521

Asia WGS AF: 0.710 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.0
DANN	Benign	0.78
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs728919; hg19: chr11-63708574;