22-45285958-C-G

Variant names:

• chr22-45285958-C-G
• NM_006953.4:c.70C>G

Variant summary

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

The NM_006953.4(UPK3A):​c.70C>G​(p.Gln24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPK3A NM_006953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15

Genes affected

UPK3A (HGNC:12580): (uroplakin 3A) This gene encodes a member of the uroplakin family, a group of transmembrane proteins that form complexes on the apical surface of the bladder epithelium. Mutations in this gene may be associated with renal adysplasia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

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
UPK3A	NM_006953.4	c.70C>G	p.Gln24Glu	missense_variant	Exon 2 of 6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.70C>G	p.Gln24Glu	missense_variant	Exon 2 of 4		NP_001161046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9	c.70C>G	p.Gln24Glu	missense_variant	Exon 2 of 6	1	NM_006953.4	ENSP00000216211.4
UPK3A	ENST00000396082.2	c.70C>G	p.Gln24Glu	missense_variant	Exon 2 of 4	1		ENSP00000379391.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70C>G (p.Q24E) alteration is located in exon 2 (coding exon 2) of the UPK3A gene. This alteration results from a C to G substitution at nucleotide position 70, causing the glutamine (Q) at amino acid position 24 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	-0.083	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.073	T;D
Sift4G	Benign	0.11	T;D
Polyphen		1.0	D;D
Vest4		0.63
MutPred		0.45		Gain of relative solvent accessibility (P = 0.025);Gain of relative solvent accessibility (P = 0.025);
MVP		0.69
MPC		0.75
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.23
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-45681839;