chr4-68816449-T-C

Variant names:

• chr4-68816449-T-C
• NM_001075.6:c.430T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001075.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	NM_001075.6	MANE Select	c.430T>C	p.Phe144Leu	missense	Exon 1 of 6	NP_001066.1	P36537-1
	UGT2B10	NM_001144767.3		c.430T>C	p.Phe144Leu	missense	Exon 1 of 6	NP_001138239.1	P36537-2
	UGT2B10	NM_001290091.2		c.-27+277T>C		intron	N/A	NP_001277020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	ENST00000265403.12	TSL:1 MANE Select	c.430T>C	p.Phe144Leu	missense	Exon 1 of 6	ENSP00000265403.7	P36537-1
	UGT2B10	ENST00000458688.2	TSL:2	c.430T>C	p.Phe144Leu	missense	Exon 1 of 6	ENSP00000413420.2	P36537-2
	UGT2B10	ENST00000878267.1		c.430T>C	p.Phe144Leu	missense	Exon 1 of 6	ENSP00000548326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		6.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.80		Loss of stability (P = 0.0492)
MVP		0.51
MPC		0.049
ClinPred		0.94	D
GERP RS		2.6
PromoterAI		0.0062	Neutral
Varity_R		0.45
gMVP		0.45
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr4-69682167;