Genetic Variant NM_001075.6:c.448G>C (chr4-68816467-G-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.448G>C(p.Asp150His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,613,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

UGT2B10
NM_001075.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32

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.448G>C	p.Asp150His	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1	P36537-1
UGT2B10	NM_001144767.3 link	c.448G>C	p.Asp150His	missense_variant	Exon 1 of 6		NP_001138239.1	P36537-2
UGT2B10	XM_017008585.3 link	c.448G>C	p.Asp150His	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2 link	c.-27+295G>C		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.448G>C	p.Asp150His	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7		P36537-1
UGT2B10	ENST00000458688.2 link	c.448G>C	p.Asp150His	missense_variant	Exon 1 of 6	2		ENSP00000413420.2		P36537-2

Frequencies

GnomAD3 genomes

AF:

0.000389

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000519

AC:

130

AN:

250674

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000524

AC:

766

AN:

1461242

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

353

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000665

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000388

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000700

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448G>C (p.D150H) alteration is located in exon 1 (coding exon 1) of the UGT2B10 gene. This alteration results from a G to C substitution at nucleotide position 448, causing the aspartic acid (D) at amino acid position 150 to be replaced by a histidine (H). 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

0.54

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0039

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.077

MutationAssessor

Pathogenic

4.1

H;H

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.7

D;D

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.79

MVP

0.62

MPC

0.059

ClinPred

0.58

GERP RS

2.6

Varity_R

0.53

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