4-68567964-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001077.4(UGT2B17):c.521G>A(p.Arg174His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,381,428 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000063 ( 0 hom., cov: 20)
Exomes 𝑓: 0.000039 ( 13 hom. )
Consequence
UGT2B17
NM_001077.4 missense
NM_001077.4 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 3.41
Genes affected
UGT2B17 (HGNC:12547): (UDP glucuronosyltransferase family 2 member B17) This gene encodes a member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Copy number variation in this gene is associated with susceptibility to osteoporosis.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UGT2B17 | NM_001077.4 | c.521G>A | p.Arg174His | missense_variant | 2/7 | ENST00000317746.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UGT2B17 | ENST00000317746.3 | c.521G>A | p.Arg174His | missense_variant | 2/7 | 1 | NM_001077.4 | P1 | |
UGT2B17 | ENST00000684088.1 | c.-26-2244G>A | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000634 AC: 8AN: 126144Hom.: 0 Cov.: 20
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GnomAD3 exomes AF: 0.0000445 AC: 9AN: 202466Hom.: 4 AF XY: 0.0000642 AC XY: 7AN XY: 108992
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GnomAD4 exome AF: 0.0000390 AC: 49AN: 1255284Hom.: 13 Cov.: 29 AF XY: 0.0000403 AC XY: 25AN XY: 621018
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GnomAD4 genome AF: 0.0000634 AC: 8AN: 126144Hom.: 0 Cov.: 20 AF XY: 0.0000498 AC XY: 3AN XY: 60186
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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 | Aug 24, 2022 | The c.521G>A (p.R174H) alteration is located in exon 1 (coding exon 1) of the UGT2B17 gene. This alteration results from a G to A substitution at nucleotide position 521, causing the arginine (R) at amino acid position 174 to be replaced by a histidine (H). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Vest4
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