chr10-121841155-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001001976.3(ATE1):ā€‹c.1084T>Gā€‹(p.Cys362Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,599,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

ATE1
NM_001001976.3 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATE1NM_001001976.3 linkuse as main transcriptc.1084T>G p.Cys362Gly missense_variant 9/12 ENST00000224652.12 NP_001001976.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATE1ENST00000224652.12 linkuse as main transcriptc.1084T>G p.Cys362Gly missense_variant 9/121 NM_001001976.3 ENSP00000224652 A1O95260-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152152
Hom.:
0
Cov.:
32
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000202
AC:
5
AN:
248026
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134192
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000445
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000173
AC:
25
AN:
1447206
Hom.:
0
Cov.:
31
AF XY:
0.0000250
AC XY:
18
AN XY:
719980
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:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000209
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74332
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000308
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000247
AC:
3

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 GeneticsMar 25, 2024The c.1084T>G (p.C362G) alteration is located in exon 9 (coding exon 9) of the ATE1 gene. This alteration results from a T to G substitution at nucleotide position 1084, causing the cysteine (C) at amino acid position 362 to be replaced by a glycine (G). 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
Uncertain
0.37
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.67
D;T;T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.92
D;D;D;D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.80
N;.;.;.;N
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-11
D;D;D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0040
D;D;D;D;D
Sift4G
Uncertain
0.011
D;D;D;D;D
Polyphen
1.0
D;D;.;D;D
Vest4
0.87
MVP
0.34
MPC
0.60
ClinPred
0.91
D
GERP RS
5.6
Varity_R
0.87
gMVP
0.84

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: rs145195524; hg19: chr10-123600670; API