Variant chr4-68816356-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001075.6(UGT2B10):c.337G>A(p.Glu113Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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 ( 0 hom. )

Consequence

UGT2B10
NM_001075.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.998

Variant links:

Genes affected

UGT2B10 (HGNC:12544): (UDP glucuronosyltransferase family 2 member B10) Predicted to be involved in lipid metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT2B10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05465895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B10	NM_001075.6 link	c.337G>A	p.Glu113Lys	missense_variant	1/6	ENST00000265403.12	NP_001066.1	P36537-1
UGT2B10	NM_001144767.3 link	c.337G>A	p.Glu113Lys	missense_variant	1/6		NP_001138239.1	P36537-2
UGT2B10	XM_017008585.3 link	c.337G>A	p.Glu113Lys	missense_variant	1/6		XP_016864074.1
UGT2B10	NM_001290091.2 link	c.-27+184G>A		intron_variant			NP_001277020.1	P36537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12 link	c.337G>A	p.Glu113Lys	missense_variant	1/6	1	NM_001075.6	ENSP00000265403.7		P36537-1
UGT2B10	ENST00000458688.2 link	c.337G>A	p.Glu113Lys	missense_variant	1/6	2		ENSP00000413420.2		P36537-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249326

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461058

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.337G>A (p.E113K) alteration is located in exon 1 (coding exon 1) of the UGT2B10 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the glutamic acid (E) at amino acid position 113 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.4

DANN

Benign

0.79

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.038

Sift

Benign

0.40

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0030

B;.

Vest4

0.13

MutPred

0.45

Gain of ubiquitination at E113 (P = 0.0162);Gain of ubiquitination at E113 (P = 0.0162);

MVP

0.33

MPC

0.0096

ClinPred

0.022

GERP RS

-0.20

Varity_R

0.036

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over