chr4-68567985-A-G

Position:

• chr4-68567985-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077.4(UGT2B17):​c.500T>C​(p.Ile167Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46

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]

ACMG classification

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
UGT2B17	NM_001077.4	c.500T>C	p.Ile167Thr	missense_variant	2/7	ENST00000317746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B17	ENST00000317746.3	c.500T>C	p.Ile167Thr	missense_variant	2/7	1	NM_001077.4	P1
UGT2B17	ENST00000684088.1	c.-26-2265T>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.500T>C (p.I167T) alteration is located in exon 1 (coding exon 1) of the UGT2B17 gene. This alteration results from a T to C substitution at nucleotide position 500, causing the isoleucine (I) at amino acid position 167 to be replaced by a threonine (T). 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	0.50
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0024	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Benign	0.038	D
Sift4G	Uncertain	0.020	D
Vest4		0.38
MutPred		0.68		Loss of stability (P = 0.0036);
MVP		0.73
MPC		0.15
ClinPred		0.93	D
GERP RS		1.4
Varity_R		0.10
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69433703;