4-68663039-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_001076.4(UGT2B15):c.974T>C(p.Ile325Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000073 ( 0 hom., cov: 20)
Exomes 𝑓: 0.0000099 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
UGT2B15
NM_001076.4 missense
NM_001076.4 missense
Scores
7
9
3
Clinical Significance
Conservation
PhyloP100: 8.31
Genes affected
UGT2B15 (HGNC:12546): (UDP glucuronosyltransferase family 2 member B15) This gene encodes a glycosyltransferase that is invovled in the metabolism and elimination of toxic compounts, both endogenous and of xenobiotic origin. This gene plays a role in the regulation of estrogens and androgens. This locus is present in a cluster of similar genes and pseudogenes on chromosome 4. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.961
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UGT2B15 | NM_001076.4 | c.974T>C | p.Ile325Thr | missense_variant | 3/6 | ENST00000338206.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UGT2B15 | ENST00000338206.6 | c.974T>C | p.Ile325Thr | missense_variant | 3/6 | 1 | NM_001076.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 136486Hom.: 0 Cov.: 20 FAILED QC
GnomAD3 genomes
?
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FAILED QC
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GnomAD3 exomes AF: 0.00000905 AC: 2AN: 221016Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 120686
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000994 AC: 14AN: 1408976Hom.: 0 Cov.: 26 AF XY: 0.00000997 AC XY: 7AN XY: 702448
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000733 AC: 1AN: 136486Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 65412
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Data not reliable, filtered out with message: AS_VQSR
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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 | Nov 09, 2022 | The c.974T>C (p.I325T) alteration is located in exon 3 (coding exon 3) of the UGT2B15 gene. This alteration results from a T to C substitution at nucleotide position 974, causing the isoleucine (I) at amino acid position 325 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0226);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at