dbSNP rs138988448: UACA:p.Gln1333Glu (chr15-70664778-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018003.4(UACA):c.3997C>G(p.Gln1333Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,613,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

UACA
NM_018003.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024314284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UACA	NM_018003.4 link	c.3997C>G	p.Gln1333Glu	missense_variant	Exon 17 of 19	ENST00000322954.11	NP_060473.2	Q9BZF9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UACA	ENST00000322954.11 link	c.3997C>G	p.Gln1333Glu	missense_variant	Exon 17 of 19	1	NM_018003.4	ENSP00000314556.6		Q9BZF9-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000798

AC:

AN:

250554

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00123

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:

0.0000281

AC:

AN:

1461124

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726886

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33438

American (AMR)

AF:

0.0000224

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111702

Other (OTH)

AF:

0.0000497

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000342

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41550

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3997C>G (p.Q1333E) 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 3997, causing the glutamine (Q) at amino acid position 1333 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

T;.;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;.;.

PhyloP100

4.8

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.44

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.24

T;T;T;T

Sift4G

Uncertain

0.043

D;T;T;T

Polyphen

0.016

B;.;.;B

Vest4

0.35

MVP

0.36

MPC

0.33

ClinPred

0.072

GERP RS

4.1

Varity_R

0.14

gMVP

0.17

Mutation Taster

=90/10

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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rs138988448

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over