Genetic Variant UNC119:c.*1C>T (chr17-28547296-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005148.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UNC119	NM_005148.4	MANE Select	c.*1C>T	3_prime_UTR	Exon 5 of 5	NP_005139.1	Q13432-1
UNC119	NM_054035.2		c.*328C>T	3_prime_UTR	Exon 4 of 4	NP_473376.1	Q13432-2
UNC119	NM_001330166.2		c.*1C>T	3_prime_UTR	Exon 6 of 6	NP_001317095.1	K7EN86

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UNC119	ENST00000335765.9	TSL:1 MANE Select	c.*1C>T	3_prime_UTR	Exon 5 of 5	ENSP00000337040.3	Q13432-1
UNC119	ENST00000301032.8	TSL:1	c.*328C>T	3_prime_UTR	Exon 4 of 4	ENSP00000301032.4	Q13432-2
UNC119	ENST00000470125.5	TSL:1	c.*328C>T	3_prime_UTR	Exon 3 of 3	ENSP00000465323.1	K7EJU3

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

GnomAD2 exomes

AF:

0.131

AC:

32839

AN:

251036

AF XY:

0.133

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 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

African (AFR)

AF:

0.0259

AC:

867

AN:

33478

American (AMR)

AF:

0.0926

AC:

4139

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

4930

AN:

26128

East Asian (EAS)

AF:

0.000277

AC:

AN:

39698

South Asian (SAS)

AF:

0.0439

AC:

3784

AN:

86254

European-Finnish (FIN)

AF:

0.193

AC:

10316

AN:

53376

Middle Eastern (MID)

AF:

0.117

AC:

676

AN:

5768

European-Non Finnish (NFE)

AF:

0.179

AC:

198535

AN:

1111872

Other (OTH)

AF:

0.152

AC:

9198

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

11926

23852

35777

47703

59629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6640

13280

19920

26560

33200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19152

AN:

152196

Hom.:

1652

Cov.:

AF XY:

0.123

AC XY:

9128

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0328

AC:

1364

AN:

41556

American (AMR)

AF:

0.117

AC:

1788

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

643

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.0385

AC:

186

AN:

4830

European-Finnish (FIN)

AF:

0.196

AC:

2073

AN:

10578

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12615

AN:

67968

Other (OTH)

AF:

0.143

AC:

302

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

833

1666

2500

3333

4166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.161

Hom.:

4826

Bravo

AF:

0.120

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.196

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Cone-rod dystrophy (1)

Idiopathic CD4 lymphocytopenia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over