rs61729919

Variant names:

• chr15-70667464-C-A
• rs61729919
• NM_018003.4:c.3220G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-70667464-C-A
• chr15-70667464-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018003.4(UACA):​c.3220G>T​(p.Asp1074Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,610,104 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: UACA NM_018003.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.60
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045127273).
• BP6: Variant 15-70667464-C-A is Benign according to our data. Variant chr15-70667464-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055452.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1643/152264) while in subpopulation AFR AF = 0.0382 (1587/41546). AF 95% confidence interval is 0.0366. There are 26 homozygotes in GnomAd4. There are 786 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

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.3220G>T	p.Asp1074Tyr	missense	Exon 16 of 19	NP_060473.2	Q9BZF9-1
	UACA	NM_001008224.3		c.3181G>T	p.Asp1061Tyr	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.3220G>T	p.Asp1074Tyr	missense	Exon 16 of 19	ENSP00000314556.6	Q9BZF9-1
	UACA	ENST00000539319.5	TSL:1	c.2893G>T	p.Asp965Tyr	missense	Exon 13 of 16	ENSP00000438667.1	F5H2B9
	UACA	ENST00000908301.1		c.3187G>T	p.Asp1063Tyr	missense	Exon 15 of 18	ENSP00000578360.1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1645 AN: 152146 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00290 AC: 717 AN: 247544 AF XY: 0.00208

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.00108 AC: 1578 AN: 1457840 Hom.: 31 Cov.: 31 AF XY: 0.000943 AC XY: 684 AN XY: 725294

African (AFR) AF: 0.0392 AC: 1303 AN: 33222

American (AMR) AF: 0.00172 AC: 76 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51444

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5752

European-Non Finnish (NFE) AF: 0.0000702 AC: 78 AN: 1111548

Other (OTH) AF: 0.00179 AC: 108 AN: 60278

GnomAD4 genome AF: 0.0108 AC: 1643 AN: 152264 Hom.: 26 Cov.: 32 AF XY: 0.0106 AC XY: 786 AN XY: 74436

African (AFR) AF: 0.0382 AC: 1587 AN: 41546

American (AMR) AF: 0.00229 AC: 35 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00445 Hom.: 16

Bravo AF: 0.0122

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0325 AC: 143

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00337 AC: 409

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.6
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.34
MVP		0.46
MPC		0.50
ClinPred		0.018	T
GERP RS		6.0
Varity_R		0.31
gMVP		0.22
Mutation Taster		=94/6	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: rs61729919; hg19: chr15-70959803;