6-79493634-CTG-TTC

Variant names:

• chr6-79493634-CTG-TTC
• NM_001122769.3:c.835_837delCAGinsGAA
• LCA5 p.Gln279Glu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

The NM_001122769.3(LCA5):​c.835_837delCAGinsGAA​(p.Gln279Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q279Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCA5 NM_001122769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

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]

LCA5 Gene-Disease associations (from GenCC):

• LCA5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000231533 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a coiled_coil_region (size 194) in uniprot entity LCA5_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_001122769.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122769.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	NM_001122769.3	MANE Select	c.835_837delCAGinsGAA	p.Gln279Glu	missense	N/A	NP_001116241.1	A0A384MDJ7
	LCA5	NM_181714.4		c.835_837delCAGinsGAA	p.Gln279Glu	missense	N/A	NP_859065.2	A0A384MDJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	ENST00000369846.9	TSL:1 MANE Select	c.835_837delCAGinsGAA	p.Gln279Glu	missense	N/A	ENSP00000358861.4	Q86VQ0
	LCA5	ENST00000392959.5	TSL:1	c.835_837delCAGinsGAA	p.Gln279Glu	missense	N/A	ENSP00000376686.1	Q86VQ0
	LCA5	ENST00000467898.3	TSL:5	c.835_837delCAGinsGAA	p.Gln279Glu	missense	N/A	ENSP00000474463.1	S4R3K6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-80203351;