4-68567947-T-G

Variant names:

• chr4-68567947-T-G
• rs1578172914
• NM_001077.4:c.538A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077.4(UGT2B17):​c.538A>C​(p.Thr180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T180A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 20)
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16070372).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	NM_001077.4	MANE Select	c.538A>C	p.Thr180Pro	missense	Exon 2 of 7	NP_001068.1	O75795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	ENST00000317746.3	TSL:1 MANE Select	c.538A>C	p.Thr180Pro	missense	Exon 2 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.538A>C	p.Thr180Pro	missense	Exon 1 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.538A>C	p.Thr180Pro	missense	Exon 1 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.62
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.16
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Benign	0.031	D
Sift4G	Benign	0.28	T
Vest4		0.26
MutPred		0.49		Gain of helix (P = 0.0199)
MVP		0.39
MPC		0.40
ClinPred		0.17	T
GERP RS		-5.3
Varity_R		0.27
gMVP		0.55
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1578172914; hg19: chr4-69433665;