NM_001077.4:c.806G>A

Variant names:

• chr4-68565639-C-T
• rs762893326
• NM_001077.4:c.806G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001077.4(UGT2B17):​c.806G>A​(p.Arg269His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,368,704 control chromosomes in the GnomAD database, including 43 homozygotes. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00013 (43 hom.)
• Consequence: UGT2B17 NM_001077.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.225
• Publications: 1 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 43 AR gene

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.806G>A	p.Arg269His	missense	Exon 3 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.806G>A	p.Arg269His	missense	Exon 3 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.806G>A	p.Arg269His	missense	Exon 2 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.806G>A	p.Arg269His	missense	Exon 2 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes AF: 0.0000161 AC: 2 AN: 123890 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000274

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: 0.0000169

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000509 AC: 10 AN: 196552 AF XY: 0.0000378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000303

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 164 AN: 1244814 Hom.: 43 Cov.: 29 AF XY: 0.000120 AC XY: 74 AN XY: 615016

African (AFR) AF: 0.00 AC: 0 AN: 30522

American (AMR) AF: 0.000134 AC: 5 AN: 37208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22610

East Asian (EAS) AF: 0.00 AC: 0 AN: 10400

South Asian (SAS) AF: 0.0000536 AC: 3 AN: 55920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4870

European-Non Finnish (NFE) AF: 0.000153 AC: 152 AN: 990860

Other (OTH) AF: 0.0000789 AC: 4 AN: 50716

GnomAD4 genome AF: 0.0000161 AC: 2 AN: 123890 Hom.: 0 Cov.: 20 AF XY: 0.0000170 AC XY: 1 AN XY: 58992

African (AFR) AF: 0.0000274 AC: 1 AN: 36452

American (AMR) AF: 0.00 AC: 0 AN: 11856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2972

East Asian (EAS) AF: 0.00 AC: 0 AN: 1332

South Asian (SAS) AF: 0.00 AC: 0 AN: 2676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59074

Other (OTH) AF: 0.00 AC: 0 AN: 1654

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000197 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	Benign	0.18
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.3
DANN	Benign	0.82
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0038	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.23
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.22
Sift	Benign	0.51	T
Sift4G	Benign	0.24	T
Vest4		0.14
MutPred		0.81		Loss of sheet (P = 0.1907)
MVP		0.13
MPC		1.1
ClinPred		0.078	T
GERP RS		0.092
Varity_R		0.029
gMVP		0.55
Mutation Taster		=97/3	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: rs762893326; hg19: chr4-69431357;