rs199714731

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005148.4(UNC119):c.65G>T(p.Gly22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,570,244 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 12 hom., cov: 31)

Exomes 𝑓: 0.00062 ( 5 hom. )

Consequence

UNC119
NM_005148.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: 2.53

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003015697).

BP6

Variant 17-28552493-C-A is Benign according to our data. Variant chr17-28552493-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 88737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-28552493-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00638 (971/152248) while in subpopulation AFR AF= 0.022 (916/41572). AF 95% confidence interval is 0.0208. There are 12 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 971 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UNC119	NM_005148.4 linkuse as main transcript	c.65G>T	p.Gly22Val	missense_variant	1/5	ENST00000335765.9	NP_005139.1
UNC119	NM_054035.2 linkuse as main transcript	c.65G>T	p.Gly22Val	missense_variant	1/4		NP_473376.1
UNC119	XM_011525459.3 linkuse as main transcript	c.65G>T	p.Gly22Val	missense_variant	1/3		XP_011523761.1
UNC119	NM_001330166.2 linkuse as main transcript	c.-249G>T		5_prime_UTR_variant	1/6		NP_001317095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC119	ENST00000335765.9 linkuse as main transcript	c.65G>T	p.Gly22Val	missense_variant	1/5	1	NM_005148.4	ENSP00000337040	P1	Q13432-1

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

962

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00160

AC:

290

AN:

181372

Hom.:

AF XY:

0.00132

AC XY:

135

AN XY:

102142

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000153

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.000618

AC:

877

AN:

1417996

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

393

AN XY:

704522

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.00169

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000968

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000855

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00638

AC:

971

AN:

152248

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

482

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.00722

ESP6500AA

AF:

0.0142

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00173

AC:

197

Asia WGS

AF:

0.00116

AC:

AN:

3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Idiopathic CD4 lymphocytopenia

Pathogenic:1Benign:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 09, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 28, 2015	- -

Cone-rod dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

0.61

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.048

D;D;D

Polyphen

0.13

B;.;.

Vest4

0.17

MVP

0.57

MPC

0.61

ClinPred

0.017

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.72

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