4-68816520-T-G

Variant names:

• chr4-68816520-T-G
• rs1479686148
• NM_001075.6:c.501T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001075.6(UGT2B10):​c.501T>G​(p.Phe167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044641078).
• BP6: Variant 4-68816520-T-G is Benign according to our data. Variant chr4-68816520-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3186170.Status of the report is criteria_provided_single_submitter, 1 stars.

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.501T>G	p.Phe167Leu	missense	Exon 1 of 6	NP_001066.1	P36537-1
	UGT2B10	NM_001144767.3		c.466+35T>G		intron	N/A	NP_001138239.1	P36537-2
	UGT2B10	NM_001290091.2		c.-27+348T>G		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.501T>G	p.Phe167Leu	missense	Exon 1 of 6	ENSP00000265403.7	P36537-1
	UGT2B10	ENST00000458688.2	TSL:2	c.466+35T>G		intron	N/A	ENSP00000413420.2	P36537-2
	UGT2B10	ENST00000878267.1		c.501T>G	p.Phe167Leu	missense	Exon 1 of 6	ENSP00000548326.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461126 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 726870

African (AFR) AF: 0.00 AC: 0 AN: 33442

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111484

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74200

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67880

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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	0.66
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0020
DANN	Benign	0.49
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	N
PhyloP100		-1.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.064
Sift	Benign	0.53	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.057
MutPred		0.51		Gain of sheet (P = 0.1208)
MVP		0.030
MPC		0.0096
ClinPred		0.11	T
GERP RS		-5.3
Varity_R		0.032
gMVP		0.18
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: rs1479686148; hg19: chr4-69682238;