chr21-39406558-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152505.4(LCA5L):c.1337G>C(p.Gly446Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,608,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152505.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCA5L | NM_152505.4 | c.1337G>C | p.Gly446Ala | missense_variant | 11/11 | ENST00000288350.8 | |
GET1-SH3BGR | NR_146618.2 | n.656-4C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCA5L | ENST00000288350.8 | c.1337G>C | p.Gly446Ala | missense_variant | 11/11 | 5 | NM_152505.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 152046Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000324 AC: 8AN: 246802Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133972
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1456300Hom.: 0 Cov.: 29 AF XY: 0.0000166 AC XY: 12AN XY: 724604
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 152046Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74252
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 2022 | The c.1337G>C (p.G446A) alteration is located in exon 10 (coding exon 7) of the LCA5L gene. This alteration results from a G to C substitution at nucleotide position 1337, causing the glycine (G) at amino acid position 446 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at