chr4-68816218-G-T

Variant names:

• chr4-68816218-G-T
• rs61750900
• NM_001075.6:c.199G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001075.6(UGT2B10):​c.199G>T​(p.Asp67Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 1,613,000 control chromosomes in the GnomAD database, including 6,576 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.068 (388 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6188 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018773675).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.199G>T	p.Asp67Tyr	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.199G>T	p.Asp67Tyr	missense_variant	Exon 1 of 6		NP_001138239.1
UGT2B10	XM_017008585.3	c.199G>T	p.Asp67Tyr	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2	c.-27+46G>T		intron_variant	Intron 1 of 5		NP_001277020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12	c.199G>T	p.Asp67Tyr	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.199G>T	p.Asp67Tyr	missense_variant	Exon 1 of 6	2		ENSP00000413420.2

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10356 AN: 151680 Hom.: 388 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0729

GnomAD2 exomes AF: 0.0649 AC: 16261 AN: 250552 AF XY: 0.0663

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0779

Gnomad EAS exome AF: 0.000710

Gnomad FIN exome AF: 0.0571

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.0711

GnomAD4 exome AF: 0.0868 AC: 126842 AN: 1461202 Hom.: 6188 Cov.: 35 AF XY: 0.0855 AC XY: 62120 AN XY: 726924

Gnomad4 AFR exome AF: 0.0386 AC: 1292 AN: 33448

Gnomad4 AMR exome AF: 0.0486 AC: 2174 AN: 44696

Gnomad4 ASJ exome AF: 0.0777 AC: 2026 AN: 26086

Gnomad4 EAS exome AF: 0.000530 AC: 21 AN: 39644

Gnomad4 SAS exome AF: 0.0414 AC: 3573 AN: 86238

Gnomad4 FIN exome AF: 0.0600 AC: 3204 AN: 53404

Gnomad4 NFE exome AF: 0.0987 AC: 109688 AN: 1111566

Gnomad4 Remaining exome AF: 0.0772 AC: 4660 AN: 60362

GnomAD4 genome AF: 0.0682 AC: 10360 AN: 151798 Hom.: 388 Cov.: 32 AF XY: 0.0661 AC XY: 4907 AN XY: 74200

Gnomad4 AFR AF: 0.0442 AC: 0.0441765 AN: 0.0441765

Gnomad4 AMR AF: 0.0646 AC: 0.0645905 AN: 0.0645905

Gnomad4 ASJ AF: 0.0652 AC: 0.0652048 AN: 0.0652048

Gnomad4 EAS AF: 0.00251 AC: 0.00251062 AN: 0.00251062

Gnomad4 SAS AF: 0.0351 AC: 0.0350768 AN: 0.0350768

Gnomad4 FIN AF: 0.0586 AC: 0.0585739 AN: 0.0585739

Gnomad4 NFE AF: 0.0928 AC: 0.0928047 AN: 0.0928047

Gnomad4 OTH AF: 0.0722 AC: 0.0721747 AN: 0.0721747

Alfa AF: 0.0637 Hom.: 125

Bravo AF: 0.0686

TwinsUK AF: 0.113 AC: 418

ALSPAC AF: 0.0968 AC: 373

ESP6500AA AF: 0.0418 AC: 184

ESP6500EA AF: 0.0917 AC: 788

ExAC AF: 0.0653 AC: 7927

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.0851

EpiControl AF: 0.0909

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.2
DANN	Benign	0.37
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.066	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.051
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.047	D;T
Polyphen		0.012	B;.
Vest4		0.073
MPC		0.024
ClinPred		0.041	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.18
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;