dbSNP rs762324444: UGT2B10:p.Pro194Ser (chr4-68816599-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001075.6(UGT2B10):c.580C>T(p.Pro194Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,612,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

UGT2B10
NM_001075.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6 link	c.580C>T	p.Pro194Ser	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1	P36537-1
UGT2B10	XM_017008585.3 link	c.580C>T	p.Pro194Ser	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001144767.3 link	c.466+114C>T		intron_variant	Intron 1 of 5		NP_001138239.1	P36537-2
UGT2B10	NM_001290091.2 link	c.-27+427C>T		intron_variant	Intron 1 of 5		NP_001277020.1	P36537

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12 link	c.580C>T	p.Pro194Ser	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7		P36537-1
UGT2B10	ENST00000458688.2 link	c.466+114C>T		intron_variant	Intron 1 of 5	2		ENSP00000413420.2		P36537-2

Frequencies

GnomAD3 genomes

AF:

0.0000791

AC:

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250356

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000970

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000123

AC:

179

AN:

1461016

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.000149

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580C>T (p.P194S) alteration is located in exon 1 (coding exon 1) of the UGT2B10 gene. This alteration results from a C to T substitution at nucleotide position 580, causing the proline (P) at amino acid position 194 to be replaced by a serine (S). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.065

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0093

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

4.3

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.32

MutPred

0.83

Loss of methylation at K199 (P = 0.0888);

MVP

0.66

MPC

0.037

ClinPred

1.0

GERP RS

2.6

Varity_R

0.33

gMVP

0.52

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