Genetic Variant UPK3A:c.-26C>T (chr22-45284988-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006953.4(UPK3A):c.-26C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

UPK3A
NM_006953.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410

Publications

0 publications found

Variant links:

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]

UPK3A Gene-Disease associations (from GenCC):

renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
renal dysplasia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
congenital anomaly of kidney and urinary tract
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

UPK3A links:

ENSG00000301739 (HGNC:):

ENSG00000301739 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UPK3A	NM_006953.4	MANE Select	c.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_008884.1	O75631-1
UPK3A	NM_006953.4	MANE Select	c.-26C>T	5_prime_UTR	Exon 1 of 6	NP_008884.1	O75631-1
UPK3A	NM_001167574.2		c.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001161046.1	O75631-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UPK3A	ENST00000216211.9	TSL:1 MANE Select	c.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000216211.4	O75631-1
UPK3A	ENST00000216211.9	TSL:1 MANE Select	c.-26C>T	5_prime_UTR	Exon 1 of 6	ENSP00000216211.4	O75631-1
UPK3A	ENST00000957030.1		c.-26C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000627089.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

125532

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1376736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30904

American (AMR)

AF:

0.00

AC:

AN:

35498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24954

East Asian (EAS)

AF:

0.00

AC:

AN:

35412

South Asian (SAS)

AF:

0.00

AC:

AN:

78796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4066

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076212

Other (OTH)

AF:

0.00

AC:

AN:

57466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.7

(source)

DANN

Uncertain

0.98

PhyloP100

-0.041

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over