4-68816470-G-T

Variant names:

• chr4-68816470-G-T
• rs200419731
• NM_001075.6:c.451G>T

Variant summary

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

The NM_001075.6(UGT2B10):​c.451G>T​(p.Ala151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,612,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A151T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574
• 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 0 ACMG points.

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.451G>T	p.Ala151Ser	missense	Exon 1 of 6	NP_001066.1	P36537-1
	UGT2B10	NM_001144767.3		c.451G>T	p.Ala151Ser	missense	Exon 1 of 6	NP_001138239.1	P36537-2
	UGT2B10	NM_001290091.2		c.-27+298G>T		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.451G>T	p.Ala151Ser	missense	Exon 1 of 6	ENSP00000265403.7	P36537-1
	UGT2B10	ENST00000458688.2	TSL:2	c.451G>T	p.Ala151Ser	missense	Exon 1 of 6	ENSP00000413420.2	P36537-2
	UGT2B10	ENST00000878267.1		c.451G>T	p.Ala151Ser	missense	Exon 1 of 6	ENSP00000548326.1

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151658 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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250530 AF XY: 0.0000516

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000139 AC: 203 AN: 1461150 Hom.: 0 Cov.: 34 AF XY: 0.000129 AC XY: 94 AN XY: 726874

African (AFR) AF: 0.000120 AC: 4 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000173 AC: 192 AN: 1111574

Other (OTH) AF: 0.000116 AC: 7 AN: 60358

GnomAD4 genome AF: 0.0000725 AC: 11 AN: 151658 Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 6 AN XY: 74046

African (AFR) AF: 0.0000242 AC: 1 AN: 41252

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.000237

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	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.78
DANN	Benign	0.73
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.57
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Benign	0.054	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.018	B
Vest4		0.18
MutPred		0.76		Loss of catalytic residue at A151 (P = 0.0983)
MVP		0.13
MPC		0.015
ClinPred		0.078	T
GERP RS		-4.2
PromoterAI		0.00050	Neutral
Varity_R		0.051
gMVP		0.24
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs200419731; hg19: chr4-69682188;