3-113722971-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_025146.4(NAA50):c.267A>G(p.Gly89=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,528,430 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (31 hom., cov: 32)
  • Exomes 𝑓: 0.024 (469 hom.)
• Consequence: NAA50 NM_025146.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.001563
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.51

Genes affected

NAA50 (HGNC:29533): (N-alpha-acetyltransferase 50, NatE catalytic subunit) Enables H4 histone acetyltransferase activity; peptide alpha-N-acetyltransferase activity; and peptidyl-lysine acetyltransferase activity. Involved in N-terminal protein amino acid acetylation; establishment of mitotic sister chromatid cohesion; and mitotic sister chromatid cohesion, centromeric. Located in cytosol and nucleus. Part of NatA complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-113722971-T-C is Benign according to our data. Variant chr3-113722971-T-C is described in ClinVar as [Benign]. Clinvar id is 3038008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0181 (2758/152254) while in subpopulation NFE AF= 0.0315 (2140/67982). AF 95% confidence interval is 0.0304. There are 31 homozygotes in gnomad4. There are 1251 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA50	NM_025146.4	c.267A>G	p.Gly89=	splice_region_variant, synonymous_variant	4/5	ENST00000240922.8
NAA50	NM_001308445.2	c.264A>G	p.Gly88=	splice_region_variant, synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA50	ENST00000240922.8	c.267A>G	p.Gly89=	splice_region_variant, synonymous_variant	4/5	1	NM_025146.4	P4

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2755 AN: 152136 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00933

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0171 AC: 3213 AN: 188292 Hom.: 52 AF XY: 0.0172 AC XY: 1757 AN XY: 101858

Gnomad AFR exome AF: 0.00441

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00498

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00806

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.0299

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0239 AC: 32831 AN: 1376176 Hom.: 469 Cov.: 30 AF XY: 0.0236 AC XY: 15995 AN XY: 678826

Gnomad4 AFR exome AF: 0.00328

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00466

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00830

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0202

GnomAD4 genome AF: 0.0181 AC: 2758 AN: 152254 Hom.: 31 Cov.: 32 AF XY: 0.0168 AC XY: 1251 AN XY: 74432

Gnomad4 AFR AF: 0.00476

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.00933

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0258 Hom.: 110

Bravo AF: 0.0167

Asia WGS AF: 0.00433 AC: 15 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NAA50-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.026
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

LitVar

Other links and lift over

dbSNP: rs34588634; hg19: chr3-113441818;