6-138908677-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001286611.2(REPS1):c.2207C>T(p.Ser736Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001286611.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251440Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135898
GnomAD4 exome AF: 0.000222 AC: 325AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.000216 AC XY: 157AN XY: 727206
GnomAD4 genome AF: 0.000125 AC: 19AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74346
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2204C>T (p.S735F) alteration is located in exon 18 (coding exon 18) of the REPS1 gene. This alteration results from a C to T substitution at nucleotide position 2204, causing the serine (S) at amino acid position 735 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 736 of the REPS1 protein (p.Ser736Phe). This variant is present in population databases (rs200224403, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with REPS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2357703). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt REPS1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at