rs2070139

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_005148.4(UNC119):c.*1C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.156 in 1,613,854 control chromosomes in the GnomAD database, including 22,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1652 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20433 hom. )

Consequence

UNC119
NM_005148.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.17

Variant links:

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]

UNC119 links:

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]

RSKR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 17-28547296-G-A is Benign according to our data. Variant chr17-28547296-G-A is described in ClinVar as [Benign]. Clinvar id is 259652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
UNC119	NM_005148.4 linkuse as main transcript	c.*1C>T	3_prime_UTR_variant	5/5	ENST00000335765.9	NP_005139.1	Q13432-1
UNC119	NM_054035.2 linkuse as main transcript	c.*328C>T	3_prime_UTR_variant	4/4		NP_473376.1	Q13432-2
UNC119	NM_001330166.2 linkuse as main transcript	c.*1C>T	3_prime_UTR_variant	6/6		NP_001317095.1	Q13432K7EN86
UNC119	XM_011525459.3 linkuse as main transcript	c.*507C>T	3_prime_UTR_variant	3/3		XP_011523761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC119	ENST00000335765 linkuse as main transcript	c.*1C>T		3_prime_UTR_variant	5/5	1	NM_005148.4	ENSP00000337040.3		Q13432-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19152

AN:

152078

Hom.:

1652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.131

AC:

32839

AN:

251036

Hom.:

2833

AF XY:

0.133

AC XY:

18030

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.0853

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0425

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.159

AC:

232456

AN:

1461658

Hom.:

20433

Cov.:

AF XY:

0.157

AC XY:

114343

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.0926

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0439

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.126

AC:

19152

AN:

152196

Hom.:

1652

Cov.:

AF XY:

0.123

AC XY:

9128

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0328

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0385

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.165

Hom.:

3807

Bravo

AF:

0.120

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.196

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Idiopathic CD4 lymphocytopenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over