NM_018003.4:c.3220G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018003.4(UACA):c.3220G>T(p.Asp1074Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,610,104 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

UACA
NM_018003.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.60

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045127273).

BP6

Variant 15-70667464-C-A is Benign according to our data. Variant chr15-70667464-C-A is described in ClinVar as [Benign]. Clinvar id is 3055452.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1643/152264) while in subpopulation AFR AF= 0.0382 (1587/41546). AF 95% confidence interval is 0.0366. There are 26 homozygotes in gnomad4. There are 786 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UACA	NM_018003.4 link	c.3220G>T	p.Asp1074Tyr	missense_variant	Exon 16 of 19	ENST00000322954.11	NP_060473.2	Q9BZF9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UACA	ENST00000322954.11 link	c.3220G>T	p.Asp1074Tyr	missense_variant	Exon 16 of 19	1	NM_018003.4	ENSP00000314556.6	Q9BZF9-1
UACA	ENST00000539319.5 link	c.2893G>T	p.Asp965Tyr	missense_variant	Exon 13 of 16	1		ENSP00000438667.1	F5H2B9
UACA	ENST00000379983.6 link	c.3181G>T	p.Asp1061Tyr	missense_variant	Exon 16 of 19	5		ENSP00000369319.2	Q9BZF9-2
UACA	ENST00000560441.5 link	c.3175G>T	p.Asp1059Tyr	missense_variant	Exon 16 of 19	5		ENSP00000454018.1	H0YNH8

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1645

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00290

AC:

717

AN:

247544

Hom.:

AF XY:

0.00208

AC XY:

279

AN XY:

133834

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00108

AC:

1578

AN:

1457840

Hom.:

Cov.:

AF XY:

0.000943

AC XY:

684

AN XY:

725294

show subpopulations

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000701

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.0108

AC:

1643

AN:

152264

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

786

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00337

AC:

409

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UACA-related disorder

Benign:1

Apr 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;.;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D;D;D

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.6

M;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.98

D;.;.;D

Vest4

0.34

MVP

0.46

MPC

0.50

ClinPred

0.018

GERP RS

6.0

Varity_R

0.31

gMVP

0.22

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