chr4-69594610-C-A

Position:

• chr4-69594610-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001105677.2(UGT2A2):​c.1198G>T​(p.Val400Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UGT2A2 NM_001105677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

Genes affected

UGT2A2 (HGNC:28183): (UDP glucuronosyltransferase family 2 member A2) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A1 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

UGT2A1 (HGNC:12542): (UDP glucuronosyltransferase family 2 member A1 complex locus) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2790889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2A2	NM_001105677.2	c.1198G>T	p.Val400Phe	missense_variant	5/6	ENST00000604629.6
UGT2A1	NM_001252275.3	c.1171G>T	p.Val391Phe	missense_variant	6/7	ENST00000286604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A2	ENST00000604629.6	c.1198G>T	p.Val400Phe	missense_variant	5/6	1	NM_001105677.2	P1
UGT2A1	ENST00000286604.9	c.1171G>T	p.Val391Phe	missense_variant	6/7	1	NM_001252275.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251274 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135806

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.80	.;T;T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D;D;D;D;.;.
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D;D;D;.;.
Sift4G	Uncertain	0.057	T;D;T;D;T;D
Polyphen		0.82	.;P;.;.;.;.
Vest4		0.32
MutPred		0.57		Loss of catalytic residue at M393 (P = 0.0373);.;.;Loss of catalytic residue at M393 (P = 0.0373);.;.;
MVP		0.30
MPC		0.042
ClinPred		0.95	D
GERP RS		-2.7
gMVP		0.55

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: rs4148304; hg19: chr4-70460328;