chr10-121790176-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001001976.3(ATE1):ā€‹c.1371A>Cā€‹(p.Pro457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,613,526 control chromosomes in the GnomAD database, including 167,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.46 ( 16319 hom., cov: 32)
Exomes š‘“: 0.45 ( 151060 hom. )

Consequence

ATE1
NM_001001976.3 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.43
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 10-121790176-T-G is Benign according to our data. Variant chr10-121790176-T-G is described in ClinVar as [Benign]. Clinvar id is 3060412.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATE1NM_001001976.3 linkuse as main transcriptc.1371A>C p.Pro457= synonymous_variant 11/12 ENST00000224652.12 NP_001001976.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATE1ENST00000224652.12 linkuse as main transcriptc.1371A>C p.Pro457= synonymous_variant 11/121 NM_001001976.3 ENSP00000224652 A1O95260-1

Frequencies

GnomAD3 genomes
AF:
0.463
AC:
70279
AN:
151852
Hom.:
16314
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.464
Gnomad AMI
AF:
0.489
Gnomad AMR
AF:
0.468
Gnomad ASJ
AF:
0.389
Gnomad EAS
AF:
0.557
Gnomad SAS
AF:
0.533
Gnomad FIN
AF:
0.474
Gnomad MID
AF:
0.421
Gnomad NFE
AF:
0.451
Gnomad OTH
AF:
0.462
GnomAD3 exomes
AF:
0.468
AC:
117508
AN:
251248
Hom.:
27763
AF XY:
0.470
AC XY:
63840
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.466
Gnomad AMR exome
AF:
0.452
Gnomad ASJ exome
AF:
0.384
Gnomad EAS exome
AF:
0.555
Gnomad SAS exome
AF:
0.530
Gnomad FIN exome
AF:
0.464
Gnomad NFE exome
AF:
0.450
Gnomad OTH exome
AF:
0.461
GnomAD4 exome
AF:
0.453
AC:
662198
AN:
1461556
Hom.:
151060
Cov.:
54
AF XY:
0.455
AC XY:
330680
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.465
Gnomad4 AMR exome
AF:
0.454
Gnomad4 ASJ exome
AF:
0.388
Gnomad4 EAS exome
AF:
0.545
Gnomad4 SAS exome
AF:
0.523
Gnomad4 FIN exome
AF:
0.468
Gnomad4 NFE exome
AF:
0.445
Gnomad4 OTH exome
AF:
0.452
GnomAD4 genome
AF:
0.463
AC:
70320
AN:
151970
Hom.:
16319
Cov.:
32
AF XY:
0.464
AC XY:
34475
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.463
Gnomad4 AMR
AF:
0.469
Gnomad4 ASJ
AF:
0.389
Gnomad4 EAS
AF:
0.557
Gnomad4 SAS
AF:
0.533
Gnomad4 FIN
AF:
0.474
Gnomad4 NFE
AF:
0.451
Gnomad4 OTH
AF:
0.459
Alfa
AF:
0.434
Hom.:
9492
Bravo
AF:
0.461
Asia WGS
AF:
0.519
AC:
1801
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 providedclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
-0.72
CADD
Benign
0.99
DANN
Benign
0.64

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

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

Other links and lift over

dbSNP: rs35350755; hg19: chr10-123549691; COSMIC: COSV56436536; API