Genetic Variant UNC119:p.Gly22Asp (chr17-28552493-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005148.4(UNC119):c.65G>A(p.Gly22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G22V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UNC119
NM_005148.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.53

Publications

8 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20760769).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC119	NM_005148.4	MANE Select	c.65G>A	p.Gly22Asp	missense	Exon 1 of 5	NP_005139.1	Q13432-1
UNC119	NM_054035.2		c.65G>A	p.Gly22Asp	missense	Exon 1 of 4	NP_473376.1	Q13432-2
UNC119	NM_001330166.2		c.-249G>A		5_prime_UTR	Exon 1 of 6	NP_001317095.1	K7EN86

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC119	ENST00000335765.9	TSL:1 MANE Select	c.65G>A	p.Gly22Asp	missense	Exon 1 of 5	ENSP00000337040.3	Q13432-1
UNC119	ENST00000301032.8	TSL:1	c.65G>A	p.Gly22Asp	missense	Exon 1 of 4	ENSP00000301032.4	Q13432-2
RSKR	ENST00000481916.6	TSL:1	n.*1195+51558G>A		intron	N/A	ENSP00000436369.2	Q96LW2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704524

African (AFR)

AF:

0.00

AC:

AN:

30364

American (AMR)

AF:

0.00

AC:

AN:

42126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25062

East Asian (EAS)

AF:

0.00

AC:

AN:

36466

South Asian (SAS)

AF:

0.00

AC:

AN:

82620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5358

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099840

Other (OTH)

AF:

0.00

AC:

AN:

58982

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

0.0038

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.4

PhyloP100

2.5

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.48

REVEL

Benign

0.23

Sift

Benign

0.036

Sift4G

Benign

0.089

Polyphen

0.041

Vest4

0.21

MutPred

0.080

Loss of glycosylation at S21 (P = 0.0398)

MVP

0.57

MPC

0.56

ClinPred

0.24

GERP RS

2.7

PromoterAI

-0.0011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.77

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over