NM_001077.4:c.1152A>C

Variant names:

• chr4-68550838-T-G
• rs13102139
• NM_001077.4:c.1152A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001077.4(UGT2B17):​c.1152A>C​(p.Ala384Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 1,248,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A384A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000024 (1 hom.)
• Consequence: UGT2B17 NM_001077.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 7 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.

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.1152A>C	p.Ala384Ala	synonymous	Exon 6 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.1152A>C	p.Ala384Ala	synonymous	Exon 6 of 7	ENSP00000320401.2	O75795
	UGT2B17	ENST00000893234.1		c.1152A>C	p.Ala384Ala	synonymous	Exon 5 of 6	ENSP00000563293.1
	UGT2B17	ENST00000950879.1		c.1020A>C	p.Ala340Ala	synonymous	Exon 4 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000240 AC: 3 AN: 1248146 Hom.: 1 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 616202

⚠️ 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: 30806

American (AMR) AF: 0.00 AC: 0 AN: 36604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22286

East Asian (EAS) AF: 0.000185 AC: 2 AN: 10790

South Asian (SAS) AF: 0.00 AC: 0 AN: 56382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993800

Other (OTH) AF: 0.00 AC: 0 AN: 50858

⚠️ 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 Cov.: 20

Alfa AF: 0.00 Hom.: 71

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.12
DANN	Benign	0.33
PhyloP100		-1.9

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: rs13102139; hg19: chr4-69416556;