chr14-88385821-G-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_StrongPS1_ModeratePM2PP5_Moderate
The NM_018418.5(SPATA7):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000237 in 1,606,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_018418.5 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000855 AC: 2AN: 233902Hom.: 0 AF XY: 0.00000789 AC XY: 1AN XY: 126780
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1454458Hom.: 0 Cov.: 31 AF XY: 0.0000235 AC XY: 17AN XY: 722734
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74364
ClinVar
Submissions by phenotype
Leber congenital amaurosis Pathogenic:1
Variant summary: SPATA7 c.3G>T (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. An alternative downstream in-frame start codon (Met 52) is located in exon 3 of the encoded protein. An activation of potential downstream translation initiation site would result in a truncated protein. At-least two other presumably pathogenic truncating variants have been reported upstream of this alternate codon in the HGMD database (example, c.20_21delTC, p.Val7Glufs*16). The variant allele was found at a frequency of 8.6e-06 in 233902 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3G>T has been reported in the literature in at-least one individual affected with Leber Congenital Amaurosis in whom a second variant was not identified (example, Perrault_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at