4-69204505-G-C

Variant names:

• chr4-69204505-G-C
• rs1721775547
• NM_001073.3:c.1235C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001073.3(UGT2B11):​c.1235C>G​(p.Ala412Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

Genes affected

UGT2B11 (HGNC:12545): (UDP glucuronosyltransferase family 2 member B11) Enables glucuronosyltransferase activity. Involved in estrogen metabolic process and xenobiotic glucuronidation. 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]

ENSG00000250696 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.1235C>G	p.Ala412Gly	missense_variant	Exon 5 of 6	ENST00000446444.2	NP_001064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.1235C>G	p.Ala412Gly	missense_variant	Exon 5 of 6	1	NM_001073.3	ENSP00000387683.1
UGT2B11	ENST00000513315.1	n.359C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
ENSG00000250696	ENST00000504301.5	n.484+3927G>C		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1	n.272+3221G>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1235C>G (p.A412G) alteration is located in exon 5 (coding exon 5) of the UGT2B11 gene. This alteration results from a C to G substitution at nucleotide position 1235, causing the alanine (A) at amino acid position 412 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.69
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.23
Sift	Benign	0.078	T
Sift4G	Benign	0.34	T
Polyphen		0.025	B
Vest4		0.27
MutPred		0.86		Loss of stability (P = 0.0499);
MVP		0.42
MPC		0.050
ClinPred		0.83	D
GERP RS		2.0
Varity_R		0.40
gMVP		0.35

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: rs1721775547; hg19: chr4-70070223;