rs34620993

Variant names:

• chr4-69102832-C-T
• rs34620993
• NM_001074.4:c.896C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001074.4(UGT2B7):​c.896C>T​(p.Ser299Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: UGT2B7 NM_001074.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01

Genes affected

UGT2B7 (HGNC:12554): (UDP glucuronosyltransferase family 2 member B7) The protein encoded by this gene belongs to the UDP-glycosyltransferase (UGT) family. UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This protein is localized in the microsome membrane, and has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.896C>T	p.Ser299Phe	missense_variant	Exon 3 of 6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.896C>T	p.Ser299Phe	missense_variant	Exon 3 of 5		NP_001317648.1
UGT2B7	NM_001349568.2	c.149C>T	p.Ser50Phe	missense_variant	Exon 4 of 7		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.896C>T	p.Ser299Phe	missense_variant	Exon 3 of 6	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000921 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	.;D;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.3	.;M;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.7	D;D;D;.
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.46, 0.59, 0.68
MutPred		0.78		.;Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);
MVP		0.58
MPC		0.20
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.92
gMVP		0.49

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: rs34620993; hg19: chr4-69968550;