chr4-68816419-A-G

Variant names:

• chr4-68816419-A-G
• rs747983652
• NM_001075.6:c.400A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001075.6(UGT2B10):​c.400A>G​(p.Lys134Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 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)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue N6-succinyllysine (size 0) in uniprot entity UDB10_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0748702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.400A>G	p.Lys134Glu	missense_variant	Exon 1 of 6	ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.400A>G	p.Lys134Glu	missense_variant	Exon 1 of 6		NP_001138239.1
UGT2B10	XM_017008585.3	c.400A>G	p.Lys134Glu	missense_variant	Exon 1 of 6		XP_016864074.1
UGT2B10	NM_001290091.2	c.-27+247A>G		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.400A>G	p.Lys134Glu	missense_variant	Exon 1 of 6	1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.400A>G	p.Lys134Glu	missense_variant	Exon 1 of 6	2		ENSP00000413420.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248816 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134988

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: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.43
DEOGEN2	Benign	0.0089	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.037
Sift	Benign	0.40	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.052	B;.
Vest4		0.078
MutPred		0.58		Loss of MoRF binding (P = 0.0029);Loss of MoRF binding (P = 0.0029);
MVP		0.31
MPC		0.011
ClinPred		0.040	T
GERP RS		-2.0
Varity_R		0.077
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs747983652; hg19: chr4-69682137;