rs146647459

Variant names:

• chr4-68560592-A-G
• rs146647459
• NM_001077.4:c.950T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-68560592-A-G
• chr4-68560592-A-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001077.4(UGT2B17):​c.950T>C​(p.Met317Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M317V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.50
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41180208).

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.950T>C	p.Met317Thr	missense	Exon 4 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.950T>C	p.Met317Thr	missense	Exon 4 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.950T>C	p.Met317Thr	missense	Exon 3 of 6	ENSP00000563293.1
	UGT2B17	ENST00000684088.1		c.200T>C	p.Met67Thr	missense	Exon 3 of 5	ENSP00000507374.1	A0A804HJ67

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 117200 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 179168 AF XY: 0.0000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000452

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 16 AN: 1213024 Hom.: 0 Cov.: 21 AF XY: 0.0000132 AC XY: 8 AN XY: 605502

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26334

American (AMR) AF: 0.0000280 AC: 1 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21652

East Asian (EAS) AF: 0.00 AC: 0 AN: 18992

South Asian (SAS) AF: 0.00 AC: 0 AN: 66526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4046

European-Non Finnish (NFE) AF: 0.0000148 AC: 14 AN: 943914

Other (OTH) AF: 0.0000203 AC: 1 AN: 49308

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 117304 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 56052

African (AFR) AF: 0.00 AC: 0 AN: 32362

American (AMR) AF: 0.00 AC: 0 AN: 11526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2794

East Asian (EAS) AF: 0.00 AC: 0 AN: 1492

South Asian (SAS) AF: 0.00 AC: 0 AN: 2440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56882

Other (OTH) AF: 0.00 AC: 0 AN: 1552

ExAC AF: 0.0000175 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.73
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		6.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.20
Sift	Benign	0.065	T
Sift4G	Uncertain	0.018	D
Vest4		0.17
MutPred		0.75		Gain of glycosylation at S312 (P = 0.0437)
MVP		0.56
MPC		1.2
ClinPred		0.31	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.47
Mutation Taster		=88/12	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: rs146647459; hg19: chr4-69426310;