Variant 12-120710530-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080533.3(UNC119B):c.56G>A(p.Gly19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,222,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

UNC119B
NM_001080533.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668

Variant links:

Genes affected

UNC119B (HGNC:16488): (unc-119 lipid binding chaperone B) Enables lipid binding activity. Involved in cilium assembly and lipoprotein transport. Located in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

UNC119B links:

UNC119B (HGNC:):

UNC119B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0550555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC119B	NM_001080533.3 linkuse as main transcript	c.56G>A	p.Gly19Glu	missense_variant	1/5	ENST00000344651.5	NP_001074002.1	A6NIH7Q69YW6
LOC124903036	XR_007063491.1 linkuse as main transcript	n.-24C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UNC119B	ENST00000344651.5 linkuse as main transcript	c.56G>A	p.Gly19Glu	missense_variant	1/5	2	NM_001080533.3	ENSP00000344942.4	A6NIH7
UNC119B	ENST00000539658.1 linkuse as main transcript	n.14G>A		non_coding_transcript_exon_variant	1/4	5		ENSP00000520658.1
UNC119B	ENST00000618898.1 linkuse as main transcript	n.73G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000386

AC:

AN:

25924

Hom.:

AF XY:

0.0000640

AC XY:

AN XY:

15632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1222066

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

597714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000207

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.56G>A (p.G19E) alteration is located in exon 1 (coding exon 1) of the UNC119B gene. This alteration results from a G to A substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.27

REVEL

Benign

0.052

Sift

Benign

0.079

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.074

MutPred

0.35

Gain of sheet (P = 0.0125);

MVP

0.043

MPC

1.7

ClinPred

0.15

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.071

gMVP

0.21

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