4-69595205-G-C

Variant names:

• chr4-69595205-G-C
• rs541627076
• NM_001105677.2:c.1068C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105677.2(UGT2A2):​c.1068C>G​(p.Asn356Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N356N) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UGT2A2 NM_001105677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18980473).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105677.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	NM_001105677.2	MANE Select	c.1068C>G	p.Asn356Lys	missense	Exon 4 of 6	NP_001099147.2	P0DTE5-1
	UGT2A1	NM_001252275.3	MANE Select	c.1041C>G	p.Asn347Lys	missense	Exon 5 of 7	NP_001239204.2	P0DTE4-5
	UGT2A1	NM_001389565.1		c.1671C>G	p.Asn557Lys	missense	Exon 6 of 8	NP_001376494.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	ENST00000604629.6	TSL:1 MANE Select	c.1068C>G	p.Asn356Lys	missense	Exon 4 of 6	ENSP00000475028.2	P0DTE5-1
	UGT2A1	ENST00000286604.9	TSL:1 MANE Select	c.1041C>G	p.Asn347Lys	missense	Exon 5 of 7	ENSP00000286604.4	P0DTE4-5
	UGT2A1	ENST00000503640.5	TSL:1	c.1041C>G	p.Asn347Lys	missense	Exon 4 of 6	ENSP00000424478.1	P0DTE4-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74448

African (AFR) AF: 0.0000241 AC: 1 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.35
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.19
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.14
Sift	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.011	B
Vest4		0.093
MutPred		0.54		Gain of methylation at N347 (P = 0.0137)
MVP		0.11
MPC		0.011
ClinPred		0.091	T
GERP RS		2.3
gMVP		0.13
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs541627076; hg19: chr4-70460923;