Genetic Variant NM_001075.6:c.132A>C (chr4-68816151-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001075.6(UGT2B10):c.132A>C(p.Glu44Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

UGT2B10
NM_001075.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.162

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6 link	c.132A>C	p.Glu44Asp	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1	P36537-1
UGT2B10	NM_001144767.3 link	c.132A>C	p.Glu44Asp	missense_variant	Exon 1 of 6		NP_001138239.1	P36537-2
UGT2B10	XM_017008585.3 link	c.132A>C	p.Glu44Asp	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2 link	c.-48A>C		5_prime_UTR_variant	Exon 1 of 6		NP_001277020.1	P36537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12 link	c.132A>C	p.Glu44Asp	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7		P36537-1
UGT2B10	ENST00000458688.2 link	c.132A>C	p.Glu44Asp	missense_variant	Exon 1 of 6	2		ENSP00000413420.2		P36537-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251142

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461320

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.132A>C (p.E44D) alteration is located in exon 1 (coding exon 1) of the UGT2B10 gene. This alteration results from a A to C substitution at nucleotide position 132, causing the glutamic acid (E) at amino acid position 44 to be replaced by an aspartic acid (D). 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

0.33

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.96

D;T

M_CAP

Benign

0.0036

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.7

H;H

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.094

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

1.0

D;.

Vest4

0.32

MutPred

0.56

Gain of MoRF binding (P = 0.1913);Gain of MoRF binding (P = 0.1913);

MVP

0.66

MPC

0.058

ClinPred

0.43

GERP RS

-2.0

Varity_R

0.12

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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