chr4-68565619-C-G

Variant names:

• chr4-68565619-C-G
• rs769625320
• NM_001077.4:c.826G>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001077.4(UGT2B17):​c.826G>C​(p.Asp276His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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.)
  • Failed GnomAD Quality Control
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27285895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B17	NM_001077.4	c.826G>C	p.Asp276His	missense_variant	Exon 3 of 7	ENST00000317746.3	NP_001068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B17	ENST00000317746.3	c.826G>C	p.Asp276His	missense_variant	Exon 3 of 7	1	NM_001077.4	ENSP00000320401.2
UGT2B17	ENST00000684088.1	c.76G>C	p.Asp26His	missense_variant	Exon 2 of 5			ENSP00000507374.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000160 AC: 2 AN: 1246262 Hom.: 1 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 615786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000537

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: 0.00

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	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Benign	0.084	T
Sift4G	Benign	0.56	T
Vest4		0.29
MutPred		0.62		Loss of stability (P = 0.0711);
MVP		0.28
MPC		1.2
ClinPred		0.52	D
GERP RS		1.8
Varity_R		0.10
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs769625320; hg19: chr4-69431337;