19-35668559-G-T

Variant names:

• chr19-35668559-G-T
• NM_007000.4:c.190G>T

Variant summary

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

The NM_007000.4(UPK1A):​c.190G>T​(p.Ala64Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: UPK1A NM_007000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45

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]

UPK1A-AS1 (HGNC:40603): (UPK1A antisense RNA 1)

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
UPK1A	NM_007000.4	c.190G>T	p.Ala64Ser	missense_variant	Exon 3 of 8	ENST00000222275.3	NP_008931.1
UPK1A	NM_001281443.2	c.190G>T	p.Ala64Ser	missense_variant	Exon 3 of 9		NP_001268372.1
UPK1A-AS1	NR_046420.1	n.184C>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPK1A	ENST00000222275.3	c.190G>T	p.Ala64Ser	missense_variant	Exon 3 of 8	1	NM_007000.4	ENSP00000222275.2
UPK1A	ENST00000379013.6	c.190G>T	p.Ala64Ser	missense_variant	Exon 2 of 8	1		ENSP00000368298.1
UPK1A-AS1	ENST00000443196.2	n.197C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.190G>T (p.A64S) alteration is located in exon 2 (coding exon 2) of the UPK1A gene. This alteration results from a G to T substitution at nucleotide position 190, causing the alanine (A) at amino acid position 64 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T;.;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T;.;.
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Uncertain	0.064	D
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	.;.;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.039	.;.;D;D
Sift4G	Benign	0.098	T;D;D;T
Polyphen		0.99	D;D;D;D
Vest4		0.46
MutPred		0.54		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.50
MPC		0.70
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.29
gMVP		0.84

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: chr19-36159461;