Variant 15-70664681-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018003.4(UACA):c.4094C>G(p.Ser1365Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,611,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

UACA
NM_018003.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

UACA (HGNC:15947): (uveal autoantigen with coiled-coil domains and ankyrin repeats) This gene encodes a protein that contains ankyrin repeats and coiled coil domains and likely plays a role in apoptosis. Studies in rodents have implicated the encoded protein in the stimulation of apoptosis and the regulation of mammary gland involution, in which the mammary gland returns to its pre-pregnant state. This protein has also been proposed to negatively regulate apoptosis based on experiments in human cell lines in which the protein was shown to interact with PRKC apoptosis WT1 regulator protein, also known as PAR-4, and inhibit translocation of the PAR-4 receptor. Autoantibodies to this protein have been identified in human patients with panuveitis and Graves' disease. Differential expression of this gene has been observed in various human cancers. [provided by RefSeq, May 2017]

UACA links:

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ACMG classification

Classification made for transcript

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=0.20881733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UACA	NM_018003.4 linkuse as main transcript	c.4094C>G	p.Ser1365Cys	missense_variant	17/19	ENST00000322954.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UACA	ENST00000322954.11 linkuse as main transcript	c.4094C>G	p.Ser1365Cys	missense_variant	17/19	1	NM_018003.4	P1	Q9BZF9-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

248344

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000262

AC:

383

AN:

1459218

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

725960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000113

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:

0.000331

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000105

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000219

EpiControl

AF:

0.000179

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2023

The c.4094C>G (p.S1365C) alteration is located in exon 17 (coding exon 17) of the UACA gene. This alteration results from a C to G substitution at nucleotide position 4094, causing the serine (S) at amino acid position 1365 to be replaced by a cysteine (C). 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

0.078

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;T;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.2

M;.;.;.

MutationTaster

Benign

0.59

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

N;N;N;D

REVEL

Benign

0.13

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.98

D;.;.;D

Vest4

0.23

MVP

0.57

MPC

0.085

ClinPred

0.12

GERP RS

4.0

Varity_R

0.13

gMVP

0.070

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over