chr10-121743784-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001976.3(ATE1):ā€‹c.1453T>Cā€‹(p.Tyr485His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ATE1
NM_001001976.3 missense

Scores

5
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATE1NM_001001976.3 linkuse as main transcriptc.1453T>C p.Tyr485His missense_variant 12/12 ENST00000224652.12 NP_001001976.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATE1ENST00000224652.12 linkuse as main transcriptc.1453T>C p.Tyr485His missense_variant 12/121 NM_001001976.3 ENSP00000224652 A1O95260-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461868
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 22, 2021The c.1453T>C (p.Y485H) alteration is located in exon 12 (coding exon 12) of the ATE1 gene. This alteration results from a T to C substitution at nucleotide position 1453, causing the tyrosine (Y) at amino acid position 485 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;T;T;T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.55
D;D;D;D;D
MetaSVM
Benign
-0.60
T
MutationTaster
Benign
0.97
N;N;N;N;N;N
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-4.5
D;D;D;D;D
REVEL
Uncertain
0.58
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
D;D;.;D;D
Vest4
0.58
MutPred
0.50
Loss of phosphorylation at Y485 (P = 0.0183);.;.;.;Loss of phosphorylation at Y485 (P = 0.0183);
MVP
0.43
MPC
0.72
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.74
gMVP
0.74

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: rs746264073; hg19: chr10-123503299; API