Genetic Variant NM_005148.4:c.*362C>G (chr17-28546935-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005148.4(UNC119):c.*362C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 342,924 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

UNC119
NM_005148.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-28546935-G-C is Benign according to our data. Variant chr17-28546935-G-C is described in ClinVar as Benign. ClinVar VariationId is 322452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 439 AD,Unknown gene.

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.*362C>G	3_prime_UTR	Exon 5 of 5	NP_005139.1	Q13432-1
UNC119	NM_054035.2		c.*689C>G	3_prime_UTR	Exon 4 of 4	NP_473376.1	Q13432-2
UNC119	NM_001330166.2		c.*362C>G	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.*362C>G	3_prime_UTR	Exon 5 of 5	ENSP00000337040.3	Q13432-1
UNC119	ENST00000301032.8	TSL:1	c.*689C>G	3_prime_UTR	Exon 4 of 4	ENSP00000301032.4	Q13432-2
UNC119	ENST00000470125.5	TSL:1	c.*689C>G	3_prime_UTR	Exon 3 of 3	ENSP00000465323.1	K7EJU3

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.000346

AC:

AN:

190628

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

AN XY:

103310

show subpopulations

African (AFR)

AF:

0.0110

AC:

AN:

5284

American (AMR)

AF:

0.000185

AC:

AN:

10804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4416

East Asian (EAS)

AF:

0.00

AC:

AN:

8292

South Asian (SAS)

AF:

0.0000780

AC:

AN:

38460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

644

European-Non Finnish (NFE)

AF:

0.0000286

AC:

AN:

104944

Other (OTH)

AF:

0.00

AC:

AN:

9282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00288

AC:

439

AN:

152296

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00989

AC:

411

AN:

41554

American (AMR)

AF:

0.000980

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00336

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-rod dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.1

(source)

DANN

Benign

0.75

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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