22-45286036-G-T

Variant names:

• chr22-45286036-G-T
• NM_006953.4:c.148G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006953.4(UPK3A):​c.148G>T​(p.Asp50Tyr) 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 pathogenic 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. D50H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPK3A NM_006953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.148G>T	p.Asp50Tyr	missense_variant	Exon 2 of 6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.148G>T	p.Asp50Tyr	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.148G>T	p.Asp50Tyr	missense_variant	Exon 2 of 6	1	NM_006953.4	ENSP00000216211.4
UPK3A	ENST00000396082.2	c.148G>T	p.Asp50Tyr	missense_variant	Exon 2 of 4	1		ENSP00000379391.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.63		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.84
MPC		0.78
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 5

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: chr22-45681917;