NM_000329.3:c.978G>T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP7BS1
This summary comes from the ClinGen Evidence Repository: The variant NM_000329.3(RPE65):c.978G>T, p.Val326= is a synonymous (silent) variant in exon 9. This variant is present in gnomAD v.4.0.0 at a GrpMax allele frequency of 0.004399, with 376 alleles/74964 total alleles in the African/African American population, which is greater than the ClinGen LCA/eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BS1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023). LINK:https://erepo.genome.network/evrepo/ui/classification/CA226597/MONDO:0100368/120
Frequency
Consequence
NM_000329.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00176 AC: 268AN: 152004Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000573 AC: 144AN: 251402Hom.: 0 AF XY: 0.000397 AC XY: 54AN XY: 135860
GnomAD4 exome AF: 0.000346 AC: 506AN: 1461780Hom.: 0 Cov.: 34 AF XY: 0.000323 AC XY: 235AN XY: 727200
GnomAD4 genome AF: 0.00178 AC: 271AN: 152122Hom.: 1 Cov.: 32 AF XY: 0.00190 AC XY: 141AN XY: 74356
ClinVar
Submissions by phenotype
not provided Benign:2Other:1
RPE65: BP4, BP7 -
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Leber congenital amaurosis 2;C3151086:Retinitis pigmentosa 20 Benign:2
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Leber congenital amaurosis 2 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Benign:1
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RPE65-related recessive retinopathy Benign:1
The variant NM_000329.3(RPE65):c.978G>T, p.Val326= is a synonymous (silent) variant in exon 9. This variant is present in gnomAD v.4.0.0 at a GrpMax allele frequency of 0.004399, with 376 alleles/74964 total alleles in the African/African American population, which is greater than the ClinGen LCA/eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BS1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023). -
Retinitis pigmentosa Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at