4-68816449-T-C

Position:

• chr4-68816449-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001075.6(UGT2B10):​c.430T>C​(p.Phe144Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.430T>C	p.Phe144Leu	missense_variant	1/6	ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.430T>C	p.Phe144Leu	missense_variant	1/6		NP_001138239.1
UGT2B10	XM_017008585.3	c.430T>C	p.Phe144Leu	missense_variant	1/6		XP_016864074.1
UGT2B10	NM_001290091.2	c.-27+277T>C		intron_variant			NP_001277020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12	c.430T>C	p.Phe144Leu	missense_variant	1/6	1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.430T>C	p.Phe144Leu	missense_variant	1/6	2		ENSP00000413420.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jan 03, 2024

The c.430T>C (p.F144L) alteration is located in exon 1 (coding exon 1) of the UGT2B10 gene. This alteration results from a T to C substitution at nucleotide position 430, causing the phenylalanine (F) at amino acid position 144 to be replaced by a leucine (L). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.9	H;H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.80		Loss of stability (P = 0.0492);Loss of stability (P = 0.0492);
MVP		0.51
MPC		0.049
ClinPred		0.94	D
GERP RS		2.6
Varity_R		0.45
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69682167;