10-121899918-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001001976.3(ATE1):​c.890G>A​(p.Arg297His) variant causes a missense change. The variant allele was found at a frequency of 0.000124 in 1,613,728 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

ATE1
NM_001001976.3 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATE1NM_001001976.3 linkuse as main transcriptc.890G>A p.Arg297His missense_variant 7/12 ENST00000224652.12 NP_001001976.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATE1ENST00000224652.12 linkuse as main transcriptc.890G>A p.Arg297His missense_variant 7/121 NM_001001976.3 ENSP00000224652 A1O95260-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152108
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251446
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000129
AC:
188
AN:
1461620
Hom.:
2
Cov.:
30
AF XY:
0.000127
AC XY:
92
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000152
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152108
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000889
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000219
EpiControl
AF:
0.000237

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 04, 2024The c.890G>A (p.R297H) alteration is located in exon 7 (coding exon 7) of the ATE1 gene. This alteration results from a G to A substitution at nucleotide position 890, causing the arginine (R) at amino acid position 297 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
Benign
0.14
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.62
D;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.0098
T
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
1.0
D;D;D;D;N;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.97
D;.
Vest4
0.61
MVP
0.43
ClinPred
0.23
T
GERP RS
6.2
Varity_R
0.31
gMVP
0.41

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: rs768017074; hg19: chr10-123659433; API