10-121743672-T-C

Position:

• chr10-121743672-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001001976.3(ATE1):​c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,597,688 control chromosomes in the GnomAD database, including 24,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (5647 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18486 hom.)
• Consequence: ATE1 NM_001001976.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.93

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-121743672-T-C is Benign according to our data. Variant chr10-121743672-T-C is described in ClinVar as [Benign]. Clinvar id is 3059476.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATE1	NM_001001976.3	c.*8A>G		3_prime_UTR_variant	12/12	ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12	c.*8A>G		3_prime_UTR_variant	12/12	1	NM_001001976.3	ENSP00000224652	A1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35538 AN: 151886 Hom.: 5631 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.197

GnomAD3 exomes AF: 0.192 AC: 45791 AN: 238390 Hom.: 6063 AF XY: 0.182 AC XY: 23499 AN XY: 128860

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0658

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.141 AC: 203411 AN: 1445684 Hom.: 18486 Cov.: 32 AF XY: 0.141 AC XY: 101414 AN XY: 718202

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0705

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.234 AC: 35608 AN: 152004 Hom.: 5647 Cov.: 32 AF XY: 0.237 AC XY: 17592 AN XY: 74292

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.207

Alfa AF: 0.137 Hom.: 755

Bravo AF: 0.251

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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	-0.90
CADD	Benign	0.95
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10886973; hg19: chr10-123503187;