4-68647238-T-A

Position:

• chr4-68647238-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001076.4(UGT2B15):​c.1459A>T​(p.Ile487Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (1 hom.)
• Consequence: UGT2B15 NM_001076.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.351

Genes affected

UGT2B15 (HGNC:12546): (UDP glucuronosyltransferase family 2 member B15) This gene encodes a glycosyltransferase that is invovled in the metabolism and elimination of toxic compounts, both endogenous and of xenobiotic origin. This gene plays a role in the regulation of estrogens and androgens. This locus is present in a cluster of similar genes and pseudogenes on chromosome 4. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09819701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B15	NM_001076.4	c.1459A>T	p.Ile487Phe	missense_variant	6/6	ENST00000338206.6	NP_001067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B15	ENST00000338206.6	c.1459A>T	p.Ile487Phe	missense_variant	6/6	1	NM_001076.4	ENSP00000341045.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461798 Hom.: 1 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.1459A>T (p.I487F) alteration is located in exon 6 (coding exon 6) of the UGT2B15 gene. This alteration results from a A to T substitution at nucleotide position 1459, causing the isoleucine (I) at amino acid position 487 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0010
DANN	Benign	0.59
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.055
Sift	Benign	0.88	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.064
MutPred		0.58		Loss of helix (P = 0.2022);
MVP		0.35
MPC		0.022
ClinPred		0.072	T
GERP RS		-1.9
Varity_R		0.049
gMVP		0.080

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69512956;