rs78551559

Variant names:

• chr15-70664767-A-G
• rs78551559
• NM_018003.4:c.4008T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_018003.4(UACA):​c.4008T>C​(p.Asn1336Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,613,628 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (68 hom.)
• Consequence: UACA NM_018003.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.512
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-70664767-A-G is Benign according to our data. Variant chr15-70664767-A-G is described in ClinVar as Benign. ClinVar VariationId is 3057193.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.512 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

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.4008T>C	p.Asn1336Asn	synonymous	Exon 17 of 19	NP_060473.2	Q9BZF9-1
	UACA	NM_001008224.3		c.3969T>C	p.Asn1323Asn	synonymous	Exon 17 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.4008T>C	p.Asn1336Asn	synonymous	Exon 17 of 19	ENSP00000314556.6	Q9BZF9-1
	UACA	ENST00000539319.5	TSL:1	c.3681T>C	p.Asn1227Asn	synonymous	Exon 14 of 16	ENSP00000438667.1	F5H2B9
	UACA	ENST00000908301.1		c.3975T>C	p.Asn1325Asn	synonymous	Exon 16 of 18	ENSP00000578360.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2467 AN: 152150 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00444 AC: 1114 AN: 250780 AF XY: 0.00336

Gnomad AFR exome AF: 0.0602

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00171 AC: 2505 AN: 1461360 Hom.: 68 Cov.: 30 AF XY: 0.00153 AC XY: 1115 AN XY: 726974

African (AFR) AF: 0.0596 AC: 1993 AN: 33436

American (AMR) AF: 0.00240 AC: 107 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00123 AC: 106 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5710

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111802

Other (OTH) AF: 0.00341 AC: 206 AN: 60358

GnomAD4 genome AF: 0.0163 AC: 2475 AN: 152268 Hom.: 61 Cov.: 32 AF XY: 0.0155 AC XY: 1155 AN XY: 74446

African (AFR) AF: 0.0575 AC: 2388 AN: 41556

American (AMR) AF: 0.00379 AC: 58 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00869 Hom.: 24

Bravo AF: 0.0179

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UACA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.68
DANN	Benign	0.48
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78551559; hg19: chr15-70957106; COSMIC: COSV105236736; COSMIC: COSV105236736;