Variant 10-121841075-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001001976.3(ATE1):c.1157+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,521,410 control chromosomes in the GnomAD database, including 20,216 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 0.13 ( 1494 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18722 hom. )

Consequence

ATE1
NM_001001976.3 splice_region, intron

Scores

Splicing: ADA: 0.00006439

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.186

Variant links:

Genes affected

ATE1 (HGNC:782): (arginyltransferase 1) This gene encodes an arginyltransferase, an enzyme that is involved in posttranslational conjugation of arginine to N-terminal aspartate or glutamate residues. Conjugation of arginine to the N-terminal aspartate or glutamate targets proteins for ubiquitin-dependent degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ATE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-121841075-A-G is Benign according to our data. Variant chr10-121841075-A-G is described in ClinVar as [Benign]. Clinvar id is 3060051.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATE1	NM_001001976.3 linkuse as main transcript	c.1157+7T>C		splice_region_variant, intron_variant		ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12 linkuse as main transcript	c.1157+7T>C		splice_region_variant, intron_variant		1	NM_001001976.3	ENSP00000224652	A1	O95260-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19929

AN:

152022

Hom.:

1491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0521

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0986

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.150

AC:

33320

AN:

221568

Hom.:

2713

AF XY:

0.151

AC XY:

18156

AN XY:

120618

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.162

AC:

221382

AN:

1369272

Hom.:

18722

Cov.:

AF XY:

0.161

AC XY:

108929

AN XY:

677182

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.213

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.131

AC:

19934

AN:

152138

Hom.:

1494

Cov.:

AF XY:

0.129

AC XY:

9597

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0520

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.0994

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.166

Hom.:

2281

Bravo

AF:

0.129

Asia WGS

AF:

0.132

AC:

458

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATE1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

-0.75

CADD

Benign

5.5

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

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