Variant 3-113723951-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025146.4(NAA50):c.145+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,569,336 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 20 hom. )

Consequence

NAA50
NM_025146.4 splice_region, intron

Scores

Splicing: ADA: 0.00002409

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0390

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-113723951-T-C is Benign according to our data. Variant chr3-113723951-T-C is described in ClinVar as [Benign]. Clinvar id is 716307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00852 (1294/151966) while in subpopulation AFR AF= 0.0232 (958/41298). AF 95% confidence interval is 0.022. There are 11 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA50	NM_025146.4 linkuse as main transcript	c.145+8A>G		splice_region_variant, intron_variant		ENST00000240922.8
NAA50	NM_001308445.2 linkuse as main transcript	c.142+8A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA50	ENST00000240922.8 linkuse as main transcript	c.145+8A>G		splice_region_variant, intron_variant		1	NM_025146.4	P4	Q9GZZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1297

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00341

AC:

766

AN:

224626

Hom.:

AF XY:

0.00316

AC XY:

385

AN XY:

121716

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.00544

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000243

Gnomad FIN exome

AF:

0.000811

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00585

GnomAD4 exome

AF:

0.00196

AC:

2776

AN:

1417370

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1371

AN XY:

702328

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.00590

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000274

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.00509

GnomAD4 genome

AF:

0.00852

AC:

1294

AN:

151966

Hom.:

Cov.:

AF XY:

0.00844

AC XY:

627

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

NAA50-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

4.2

Dann

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

SpliceAI score (max)

0.18

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