NM_001122769.3:c.835C>G

Variant names:

• chr6-79493636-G-C
• NM_001122769.3:c.835C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001122769.3(LCA5):​c.835C>G​(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. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCA5 NM_001122769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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 Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a coiled_coil_region (size 194) in uniprot entity LCA5_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_001122769.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3116548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCA5	NM_001122769.3	c.835C>G	p.Gln279Glu	missense_variant	Exon 4 of 8	ENST00000369846.9	NP_001116241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCA5	ENST00000369846.9	c.835C>G	p.Gln279Glu	missense_variant	Exon 4 of 8	1	NM_001122769.3	ENSP00000358861.4
LCA5	ENST00000392959.5	c.835C>G	p.Gln279Glu	missense_variant	Exon 5 of 9	1		ENSP00000376686.1
LCA5	ENST00000467898.3	c.835C>G	p.Gln279Glu	missense_variant	Exon 4 of 7	5		ENSP00000474463.1
ENSG00000231533	ENST00000652956.1	n.469+12196G>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.089	T;T;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.56	.;T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.23
Sift	Benign	0.16	T;T;.
Sift4G	Benign	0.48	T;T;T
Polyphen		0.86	P;P;.
Vest4		0.28
MutPred		0.13		Loss of MoRF binding (P = 0.03);Loss of MoRF binding (P = 0.03);Loss of MoRF binding (P = 0.03);
MVP		0.79
MPC		0.096
ClinPred		0.65	D
GERP RS		5.6
Varity_R		0.11
gMVP		0.054

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-80203353;