chr15-70667301-A-C

Position:

• chr15-70667301-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000322954.11(UACA):​c.3383T>G​(p.Ile1128Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UACA ENST00000322954.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39767525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UACA	NM_018003.4	c.3383T>G	p.Ile1128Ser	missense_variant	16/19	ENST00000322954.11	NP_060473.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UACA	ENST00000322954.11	c.3383T>G	p.Ile1128Ser	missense_variant	16/19	1	NM_018003.4	ENSP00000314556	P1
UACA	ENST00000539319.5	c.3056T>G	p.Ile1019Ser	missense_variant	13/16	1		ENSP00000438667
UACA	ENST00000379983.6	c.3344T>G	p.Ile1115Ser	missense_variant	16/19	5		ENSP00000369319
UACA	ENST00000560441.5	c.3338T>G	p.Ile1113Ser	missense_variant	16/19	5		ENSP00000454018

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.3383T>G (p.I1128S) alteration is located in exon 16 (coding exon 16) of the UACA gene. This alteration results from a T to G substitution at nucleotide position 3383, causing the isoleucine (I) at amino acid position 1128 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M;.;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.18	T;T;T;D
Polyphen		0.94	P;.;.;D
Vest4		0.55
MutPred		0.15		Gain of phosphorylation at I1128 (P = 0.0546);.;.;.;
MVP		0.62
MPC		0.23
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.42
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-70959640;