6-79487422-G-T

Variant names:

• chr6-79487422-G-T
• rs766143193
• NM_001122769.3:c.1676C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001122769.3(LCA5):​c.1676C>A​(p.Ser559*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCA5 NM_001122769.3 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.27

Genes affected

LCA5 (HGNC:31923): (lebercilin LCA5) This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]

ENSG00000231533 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-79487422-G-T is Pathogenic according to our data. Variant chr6-79487422-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 438152.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-79487422-G-T is described in Lovd as [Pathogenic]. Variant chr6-79487422-G-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCA5	NM_001122769.3	c.1676C>A	p.Ser559*	stop_gained	Exon 8 of 8	ENST00000369846.9	NP_001116241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCA5	ENST00000369846.9	c.1676C>A	p.Ser559*	stop_gained	Exon 8 of 8	1	NM_001122769.3	ENSP00000358861.4
LCA5	ENST00000392959.5	c.1676C>A	p.Ser559*	stop_gained	Exon 9 of 9	1		ENSP00000376686.1
ENSG00000231533	ENST00000652956.1	n.469+5982G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Leber congenital amaurosis Pathogenic:1

Jan 01, 2015

NIHR Bioresource Rare Diseases, University of Cambridge

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.28
GERP RS		5.9

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

Other links and lift over

dbSNP: rs766143193; hg19: chr6-80197139;