19-9967905-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000264828.4(COL5A3):c.4403C>T(p.Pro1468Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000264828.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A3 | NM_015719.4 | c.4403C>T | p.Pro1468Leu | missense_variant, splice_region_variant | 61/67 | ENST00000264828.4 | NP_056534.2 | |
COL5A3 | XM_011528042.3 | c.4400C>T | p.Pro1467Leu | missense_variant, splice_region_variant | 61/67 | XP_011526344.1 | ||
COL5A3 | XM_017026849.2 | c.2066C>T | p.Pro689Leu | missense_variant, splice_region_variant | 34/40 | XP_016882338.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A3 | ENST00000264828.4 | c.4403C>T | p.Pro1468Leu | missense_variant, splice_region_variant | 61/67 | 1 | NM_015719.4 | ENSP00000264828 | P1 | |
COL5A3 | ENST00000461214.1 | n.496C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 249796Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135124
GnomAD4 exome AF: 0.0000705 AC: 103AN: 1460868Hom.: 0 Cov.: 31 AF XY: 0.0000784 AC XY: 57AN XY: 726686
GnomAD4 genome AF: 0.000112 AC: 17AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74440
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.4403C>T (p.P1468L) alteration is located in exon 61 (coding exon 61) of the COL5A3 gene. This alteration results from a C to T substitution at nucleotide position 4403, causing the proline (P) at amino acid position 1468 to be replaced by a leucine (L). 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