22-45285978-C-G

Variant names:

• chr22-45285978-C-G
• rs199656309
• NM_006953.4:c.90C>G

Variant summary

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

The NM_006953.4(UPK3A):​c.90C>G​(p.Phe30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UPK3A NM_006953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17906955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPK3A	NM_006953.4	c.90C>G	p.Phe30Leu	missense_variant	Exon 2 of 6	ENST00000216211.9	NP_008884.1
UPK3A	NM_001167574.2	c.90C>G	p.Phe30Leu	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.90C>G	p.Phe30Leu	missense_variant	Exon 2 of 6	1	NM_006953.4	ENSP00000216211.4
UPK3A	ENST00000396082.2	c.90C>G	p.Phe30Leu	missense_variant	Exon 2 of 4	1		ENSP00000379391.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	0.020
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.53
Sift	Benign	0.28	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.94	P;D
Vest4		0.33
MutPred		0.53		Loss of catalytic residue at F30 (P = 0.062);Loss of catalytic residue at F30 (P = 0.062);
MVP		0.23
MPC		0.23
ClinPred		0.86	D
GERP RS		-5.9
Varity_R		0.081
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199656309; hg19: chr22-45681859;