chr15-70664801-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018003.4(UACA):āc.3974T>Gā(p.Leu1325Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,612,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
UACA
NM_018003.4 missense
NM_018003.4 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 6.48
Genes affected
UACA (HGNC:15947): (uveal autoantigen with coiled-coil domains and ankyrin repeats) This gene encodes a protein that contains ankyrin repeats and coiled coil domains and likely plays a role in apoptosis. Studies in rodents have implicated the encoded protein in the stimulation of apoptosis and the regulation of mammary gland involution, in which the mammary gland returns to its pre-pregnant state. This protein has also been proposed to negatively regulate apoptosis based on experiments in human cell lines in which the protein was shown to interact with PRKC apoptosis WT1 regulator protein, also known as PAR-4, and inhibit translocation of the PAR-4 receptor. Autoantibodies to this protein have been identified in human patients with panuveitis and Graves' disease. Differential expression of this gene has been observed in various human cancers. [provided by RefSeq, May 2017]
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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 | UniProt |
---|---|---|---|---|---|---|---|
UACA | NM_018003.4 | c.3974T>G | p.Leu1325Arg | missense_variant | 17/19 | ENST00000322954.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UACA | ENST00000322954.11 | c.3974T>G | p.Leu1325Arg | missense_variant | 17/19 | 1 | NM_018003.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249492Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134916
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1459854Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 726304
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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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 submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.3974T>G (p.L1325R) alteration is located in exon 17 (coding exon 17) of the UACA gene. This alteration results from a T to G substitution at nucleotide position 3974, causing the leucine (L) at amino acid position 1325 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0241);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at