Genetic Variant NM_005148.4:c.*83G>A (chr17-28547214-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005148.4(UNC119):c.*83G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

UNC119
NM_005148.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.*83G>A	3_prime_UTR	Exon 5 of 5	NP_005139.1	Q13432-1
UNC119	NM_054035.2		c.*410G>A	3_prime_UTR	Exon 4 of 4	NP_473376.1	Q13432-2
UNC119	NM_001330166.2		c.*83G>A	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.*83G>A	3_prime_UTR	Exon 5 of 5	ENSP00000337040.3	Q13432-1
UNC119	ENST00000301032.8	TSL:1	c.*410G>A	3_prime_UTR	Exon 4 of 4	ENSP00000301032.4	Q13432-2
UNC119	ENST00000470125.5	TSL:1	c.*410G>A	3_prime_UTR	Exon 3 of 3	ENSP00000465323.1	K7EJU3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1390810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693254

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31836

American (AMR)

AF:

0.00

AC:

AN:

40224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25338

East Asian (EAS)

AF:

0.00

AC:

AN:

38090

South Asian (SAS)

AF:

0.00

AC:

AN:

82832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

9.45e-7

AC:

AN:

1058536

Other (OTH)

AF:

0.00

AC:

AN:

57898

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.4

(source)

DANN

Benign

0.55

PhyloP100

-0.063

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over