chr4-68567830-G-T

Variant names:

• chr4-68567830-G-T
• rs143693642
• NM_001077.4:c.655C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077.4(UGT2B17):​c.655C>A​(p.Leu219Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,245,522 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000016 (1 hom.)
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33787778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B17	NM_001077.4	c.655C>A	p.Leu219Ile	missense_variant	Exon 2 of 7	ENST00000317746.3	NP_001068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B17	ENST00000317746.3	c.655C>A	p.Leu219Ile	missense_variant	Exon 2 of 7	1	NM_001077.4	ENSP00000320401.2
UGT2B17	ENST00000684088.1	c.-26-2110C>A		intron_variant	Intron 1 of 4			ENSP00000507374.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.0000103 AC: 2 AN: 194156 Hom.: 1 AF XY: 0.0000191 AC XY: 2 AN XY: 104704

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1245522 Hom.: 1 Cov.: 29 AF XY: 0.00000325 AC XY: 2 AN XY: 616124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000202

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Vest4		0.11
MutPred		0.66		Gain of catalytic residue at L219 (P = 0.0066);
MVP		0.27
MPC		0.17
ClinPred		0.31	T
GERP RS		2.7
Varity_R		0.058
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs143693642; hg19: chr4-69433548;