4-69096663-A-T

Variant names:

• chr4-69096663-A-T
• NM_001074.4:c.143A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001074.4(UGT2B7):​c.143A>T​(p.Gln48Leu) 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. 14/21 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: UGT2B7 NM_001074.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.396

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17980224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.143A>T	p.Gln48Leu	missense_variant	Exon 1 of 6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.143A>T	p.Gln48Leu	missense_variant	Exon 1 of 5		NP_001317648.1
UGT2B7	NM_001349568.2	c.-26-1877A>T		intron_variant	Intron 2 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.143A>T	p.Gln48Leu	missense_variant	Exon 1 of 6	1	NM_001074.4	ENSP00000304811.7

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

Feb 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143A>T (p.Q48L) alteration is located in exon 1 (coding exon 1) of the UGT2B7 gene. This alteration results from a A to T substitution at nucleotide position 143, causing the glutamine (Q) at amino acid position 48 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.40	T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.30	T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.7	D;D;.
REVEL	Benign	0.054
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.23	T;T;T
Polyphen		0.031	B;B;.
Vest4		0.15
MutPred		0.39		Loss of disorder (P = 0.2974);Loss of disorder (P = 0.2974);Loss of disorder (P = 0.2974);
MVP		0.088
MPC		0.024
ClinPred		0.44	T
GERP RS		-0.57
Varity_R		0.27
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69962381;