NM_021729.6:c.65T>C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_021729.6(VPS11):āc.65T>Cā(p.Leu22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,590,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_021729.6 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS11 | NM_021729.6 | c.65T>C | p.Leu22Pro | missense_variant | Exon 1 of 16 | ENST00000621676.5 | NP_068375.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS11 | ENST00000621676.5 | c.65T>C | p.Leu22Pro | missense_variant | Exon 1 of 16 | 1 | NM_021729.6 | ENSP00000481126.1 | ||
VPS11 | ENST00000614944 | c.-181T>C | 5_prime_UTR_variant | Exon 1 of 16 | 2 | ENSP00000481807.1 | ||||
VPS11 | ENST00000622309.4 | n.66T>C | non_coding_transcript_exon_variant | Exon 1 of 13 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000474 AC: 1AN: 210976Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 114412
GnomAD4 exome AF: 0.00000278 AC: 4AN: 1437848Hom.: 0 Cov.: 31 AF XY: 0.00000421 AC XY: 3AN XY: 713254
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74496
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.65T>C (p.L22P) alteration is located in exon 1 (coding exon 1) of the VPS11 gene. This alteration results from a T to C substitution at nucleotide position 65, causing the leucine (L) at amino acid position 22 to be replaced by a proline (P). 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