rs1057353

Positions:

• chr22-45287423-G-A
• chr22-45287423-G-C
• chr22-45287423-G-T

Variant summary

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

The NM_006953.4(UPK3A):​c.460G>A​(p.Ala154Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A154P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPK3A NM_006953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28054535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.460G>A	p.Ala154Thr	missense_variant	3/6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.208+1327G>A		intron_variant			NP_001161046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPK3A	ENST00000216211.9	c.460G>A	p.Ala154Thr	missense_variant	3/6	1	NM_006953.4	ENSP00000216211	P1
UPK3A	ENST00000396082.2	c.208+1327G>A		intron_variant		1		ENSP00000379391

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.066
Sift	Benign	0.065	T
Sift4G	Uncertain	0.029	D
Polyphen		0.49	P
Vest4		0.15
MutPred		0.33		Loss of stability (P = 0.1061);
MVP		0.50
MPC		0.21
ClinPred		0.54	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1057353; hg19: chr22-45683304;