Variant 3-113722971-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_025146.4(NAA50):c.267A>G(p.Gly89Gly) 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 (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: 3.51

Variant links:

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]

NAA50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 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 no_assertion_criteria_provided, 0 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 GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA50	NM_025146.4 linkuse as main transcript	c.267A>G	p.Gly89Gly	splice_region_variant, synonymous_variant	4/5	ENST00000240922.8	NP_079422.1	Q9GZZ1-1
NAA50	NM_001308445.2 linkuse as main transcript	c.264A>G	p.Gly88Gly	splice_region_variant, synonymous_variant	4/5		NP_001295374.1	E7EQ69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA50	ENST00000240922.8 linkuse as main transcript	c.267A>G	p.Gly89Gly	splice_region_variant, synonymous_variant	4/5	1	NM_025146.4	ENSP00000240922.2		Q9GZZ1-1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2755

AN:

152136

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0172

AC XY:

1757

AN XY:

101858

show subpopulations

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.:

AF XY:

0.0236

AC XY:

15995

AN XY:

678826

show subpopulations

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.:

Cov.:

AF XY:

0.0168

AC XY:

1251

AN XY:

74432

show subpopulations

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:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NAA50-related disorder

Benign:1

Benign, no assertion criteria provided

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over