19-35675904-C-T

Variant names:

• chr19-35675904-C-T
• NM_007000.4:c.533C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007000.4(UPK1A):​c.533C>T​(p.Ala178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UPK1A NM_007000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

Genes affected

UPK1A (HGNC:12577): (uroplakin 1A) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is found in the asymmetrical unit membrane (AUM) where it can complex with other transmembrane 4 superfamily proteins. It may play a role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions. The protein may also play a role in tumor suppression. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14570251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK1A	NM_007000.4	c.533C>T	p.Ala178Val	missense_variant	Exon 6 of 8	ENST00000222275.3	NP_008931.1
UPK1A	NM_001281443.2	c.533C>T	p.Ala178Val	missense_variant	Exon 6 of 9		NP_001268372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK1A	ENST00000222275.3	c.533C>T	p.Ala178Val	missense_variant	Exon 6 of 8	1	NM_007000.4	ENSP00000222275.2
UPK1A	ENST00000379013.6	c.533C>T	p.Ala178Val	missense_variant	Exon 5 of 8	1		ENSP00000368298.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461608 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727102

Gnomad4 AFR exome AF: 0.0000597

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T;.;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.74	T;T;.;.
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	-0.34	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.70	.;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.60	.;.;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.072	B;P;P;B
Vest4		0.29
MutPred		0.33		Loss of methylation at R176 (P = 0.0813);Loss of methylation at R176 (P = 0.0813);Loss of methylation at R176 (P = 0.0813);Loss of methylation at R176 (P = 0.0813);
MVP		0.42
MPC		0.26
ClinPred		0.35	T
GERP RS		5.0
Varity_R		0.11
gMVP		0.34

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: chr19-36166806;