rs61750900

Positions:

• chr4-68816218-G-A
• chr4-68816218-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001075.6(UGT2B10):​c.199G>A​(p.Asp67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030833274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B10	NM_001075.6	c.199G>A	p.Asp67Asn	missense_variant	1/6	ENST00000265403.12
UGT2B10	NM_001144767.3	c.199G>A	p.Asp67Asn	missense_variant	1/6
UGT2B10	XM_017008585.3	c.199G>A	p.Asp67Asn	missense_variant	1/6
UGT2B10	NM_001290091.2	c.-27+46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B10	ENST00000265403.12	c.199G>A	p.Asp67Asn	missense_variant	1/6	1	NM_001075.6	P1
UGT2B10	ENST00000458688.2	c.199G>A	p.Asp67Asn	missense_variant	1/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000798 AC: 2 AN: 250552 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135506

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461218 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 726930

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.65
DANN	Benign	0.62
DEOGEN2	Benign	0.0026	T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.051	T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.82	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.013
Sift	Benign	0.36	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0020	B;.
Vest4		0.096
MutPred		0.34		Gain of ubiquitination at K72 (P = 0.0773);Gain of ubiquitination at K72 (P = 0.0773);
MVP		0.14
MPC		0.0095
ClinPred		0.081	T
GERP RS		-4.4
Varity_R		0.025
gMVP		0.064

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

LitVar

Other links and lift over

dbSNP: rs61750900; hg19: chr4-69681936;