rs376705053

Variant names:

• chr15-70667067-G-A
• rs376705053
• NM_018003.4:c.3617C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-70667067-G-A
• chr15-70667067-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018003.4(UACA):​c.3617C>T​(p.Ser1206Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,130 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (1 hom.)
• Consequence: UACA NM_018003.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013677418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UACA	NM_018003.4	c.3617C>T	p.Ser1206Leu	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.3617C>T	p.Ser1206Leu	missense_variant	Exon 16 of 19	1	NM_018003.4	ENSP00000314556.6
UACA	ENST00000539319.5	c.3290C>T	p.Ser1097Leu	missense_variant	Exon 13 of 16	1		ENSP00000438667.1
UACA	ENST00000379983.6	c.3578C>T	p.Ser1193Leu	missense_variant	Exon 16 of 19	5		ENSP00000369319.2
UACA	ENST00000560441.5	c.3572C>T	p.Ser1191Leu	missense_variant	Exon 16 of 19	5		ENSP00000454018.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000188 AC: 47 AN: 250584 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000602 AC: 88 AN: 1461176 Hom.: 1 Cov.: 31 AF XY: 0.0000426 AC XY: 31 AN XY: 726888

African (AFR) AF: 0.0000299 AC: 1 AN: 33442

American (AMR) AF: 0.00114 AC: 51 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111892

Other (OTH) AF: 0.0000828 AC: 5 AN: 60384

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151954 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74196

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.000263 AC: 4 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3617C>T (p.S1206L) 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 3617, causing the serine (S) at amino acid position 1206 to be replaced by a leucine (L). 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	0.070
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T;.;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.014	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;.;.;.
PhyloP100		1.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.061	T;D;T;D
Sift4G	Uncertain	0.027	D;D;D;D
Polyphen		0.0050	B;.;.;B
Vest4		0.064
MVP		0.23
MPC		0.077
ClinPred		0.024	T
GERP RS		1.2
Varity_R		0.066
gMVP		0.089
Mutation Taster		=84/16	polymorphism

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

dbSNP: rs376705053; hg19: chr15-70959406; COSMIC: COSV108107145; COSMIC: COSV108107145;