NM_018003.4:c.3480G>T

Variant names:

• chr15-70667204-C-A
• NM_018003.4:c.3480G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018003.4(UACA):​c.3480G>T​(p.Lys1160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 0.485
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13266477).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018003.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UACA	NM_018003.4	MANE Select	c.3480G>T	p.Lys1160Asn	missense	Exon 16 of 19	NP_060473.2	Q9BZF9-1
	UACA	NM_001008224.3		c.3441G>T	p.Lys1147Asn	missense	Exon 16 of 19	NP_001008225.1	Q9BZF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UACA	ENST00000322954.11	TSL:1 MANE Select	c.3480G>T	p.Lys1160Asn	missense	Exon 16 of 19	ENSP00000314556.6	Q9BZF9-1
	UACA	ENST00000539319.5	TSL:1	c.3153G>T	p.Lys1051Asn	missense	Exon 13 of 16	ENSP00000438667.1	F5H2B9
	UACA	ENST00000908301.1		c.3447G>T	p.Lys1149Asn	missense	Exon 15 of 18	ENSP00000578360.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.0031
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.48
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.14		Loss of ubiquitination at K1160 (P = 0.0051)
MVP		0.48
MPC		0.35
ClinPred		0.96	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.16

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

Other links and lift over

hg19: chr15-70959543; COSMIC: COSV108107211; COSMIC: COSV108107211;