NM_018003.4:c.3743C>T

Variant names:

• chr15-70666941-G-A
• NM_018003.4:c.3743C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018003.4(UACA):​c.3743C>T​(p.Ala1248Val) 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 NM_018003.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16519713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UACA	NM_018003.4	c.3743C>T	p.Ala1248Val	missense_variant	Exon 16 of 19	ENST00000322954.11	NP_060473.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UACA	ENST00000322954.11	c.3743C>T	p.Ala1248Val	missense_variant	Exon 16 of 19	1	NM_018003.4	ENSP00000314556.6
UACA	ENST00000539319.5	c.3416C>T	p.Ala1139Val	missense_variant	Exon 13 of 16	1		ENSP00000438667.1
UACA	ENST00000379983.6	c.3704C>T	p.Ala1235Val	missense_variant	Exon 16 of 19	5		ENSP00000369319.2
UACA	ENST00000560441.5	c.3698C>T	p.Ala1233Val	missense_variant	Exon 16 of 19	5		ENSP00000454018.1

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

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3743C>T (p.A1248V) alteration is located in exon 16 (coding exon 16) of the UACA gene. This alteration results from a C to T substitution at nucleotide position 3743, causing the alanine (A) at amino acid position 1248 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.043	D;D;D;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.85	P;.;.;P
Vest4		0.25
MutPred		0.14		Loss of ubiquitination at K1246 (P = 0.0605);.;.;.;
MVP		0.54
MPC		0.19
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.082

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: chr15-70959280;