17-28547071-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005148.4(UNC119):c.*226C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 537,970 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (3 hom.)
• Consequence: UNC119 NM_005148.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.603

Genes affected

UNC119 (HGNC:12565): (unc-119 lipid binding chaperone) This gene is specifically expressed in the photoreceptors in the retina. The encoded product shares strong homology with the C. elegans unc119 protein and it can functionally complement the C. elegans unc119 mutation. It has been localized to the photoreceptor synapses in the outer plexiform layer of the retina, and suggested to play a role in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-28547071-G-A is Benign according to our data. Variant chr17-28547071-G-A is described in ClinVar as [Benign]. Clinvar id is 322455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC119	NM_005148.4	c.*226C>T		3_prime_UTR_variant	5/5	ENST00000335765.9
UNC119	NM_001330166.2	c.*226C>T		3_prime_UTR_variant	6/6
UNC119	NM_054035.2	c.*553C>T		3_prime_UTR_variant	4/4
UNC119	XM_011525459.3	c.*732C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC119	ENST00000335765.9	c.*226C>T		3_prime_UTR_variant	5/5	1	NM_005148.4	P1

Frequencies

GnomAD3 genomes AF: 0.000592 AC: 90 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000775 AC: 299 AN: 385714 Hom.: 3 Cov.: 4 AF XY: 0.000768 AC XY: 158 AN XY: 205856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000508

Gnomad4 ASJ exome AF: 0.000176

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.000415

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000439

Gnomad4 OTH exome AF: 0.000568

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000672 AC XY: 50 AN XY: 74456

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000946

Bravo AF: 0.000808

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-rod dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.62
Dann	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs80000715; hg19: chr17-26874089;