NM_018003.4:c.4007A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_018003.4(UACA):c.4007A>G(p.Asn1336Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,613,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. N1336N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

UACA
NM_018003.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.33

Publications

4 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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008372039).

BP6

Variant 15-70664768-T-C is Benign according to our data. Variant chr15-70664768-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3047143.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UACA	NM_018003.4 link	c.4007A>G	p.Asn1336Ser	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.4007A>G	p.Asn1336Ser	missense_variant	Exon 17 of 19	1	NM_018003.4	ENSP00000314556.6		Q9BZF9-1

Frequencies

GnomAD3 genomes

AF:

0.000894

AC:

136

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000223

AC:

AN:

250794

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461368

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.00302

AC:

101

AN:

33446

American (AMR)

AF:

0.000157

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39668

South Asian (SAS)

AF:

0.000139

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111800

Other (OTH)

AF:

0.000199

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000900

AC:

137

AN:

152280

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41564

American (AMR)

AF:

0.000327

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000354

Hom.:

Bravo

AF:

0.00109

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UACA-related disorder

Benign:1

Feb 27, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.58

D;.;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.0084

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;.;.

PhyloP100

1.3

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.5

D;D;D;D

REVEL

Benign

0.062

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.010

B;.;.;B

Vest4

0.20

MVP

0.42

MPC

0.070

ClinPred

0.0072

GERP RS

-1.2

Varity_R

0.080

gMVP

0.16

Mutation Taster

=100/0

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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NM_018003.4:c.4007A>G

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