22-45286090-G-T

Position:

• chr22-45286090-G-T

Variant summary

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

The NM_006953.4(UPK3A):​c.202G>T​(p.Asp68Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D68N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UPK3A NM_006953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.202G>T	p.Asp68Tyr	missense_variant	2/6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.202G>T	p.Asp68Tyr	missense_variant	2/4		NP_001161046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9	c.202G>T	p.Asp68Tyr	missense_variant	2/6	1	NM_006953.4	ENSP00000216211.4
UPK3A	ENST00000396082.2	c.202G>T	p.Asp68Tyr	missense_variant	2/4	1		ENSP00000379391.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727202

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.98	D;P
Vest4		0.63
MutPred		0.37		Gain of catalytic residue at L63 (P = 0.093);Gain of catalytic residue at L63 (P = 0.093);
MVP		0.63
MPC		0.78
ClinPred		0.93	D
GERP RS		2.8
Varity_R		0.15
gMVP		0.73

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: chr22-45681971;