rs4095564

Variant names:

• chr4-68827385-G-A
• rs4095564
• NM_001075.6:c.1144G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001075.6(UGT2B10):​c.1144G>A​(p.Ala382Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

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.1144G>A	p.Ala382Thr	missense	Exon 5 of 6	NP_001066.1
	UGT2B10	NM_001144767.3		c.892G>A	p.Ala298Thr	missense	Exon 5 of 6	NP_001138239.1
	UGT2B10	NM_001290091.2		c.400G>A	p.Ala134Thr	missense	Exon 5 of 6	NP_001277020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	ENST00000265403.12	TSL:1 MANE Select	c.1144G>A	p.Ala382Thr	missense	Exon 5 of 6	ENSP00000265403.7
	UGT2B10	ENST00000458688.2	TSL:2	c.892G>A	p.Ala298Thr	missense	Exon 5 of 6	ENSP00000413420.2
	UGT2B10	ENST00000878267.1		c.1135G>A	p.Ala379Thr	missense	Exon 5 of 6	ENSP00000548326.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461244 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726934

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111550

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74198

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0053	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		6.6
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.82		Gain of catalytic residue at A382 (P = 0.0814)
MVP		0.56
MPC		0.060
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.25
gMVP		0.30
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs4095564; hg19: chr4-69693103;