22-50674600-TTCCCCGGCGCGAGCGGCCCCGGCCCGG-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001372044.2(SHANK3):c.185_211delTCCCCGGCGCGAGCGGCCCCGGCCCGG(p.Phe62_Gly71delinsCys) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_001372044.2 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHANK3 | NM_001372044.2 | c.185_211delTCCCCGGCGCGAGCGGCCCCGGCCCGG | p.Phe62_Gly71delinsCys | disruptive_inframe_deletion | Exon 3 of 25 | NP_001358973.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHANK3 | ENST00000692848 | c.-41_-15delTCCCCGGCGCGAGCGGCCCCGGCCCGG | 5_prime_UTR_variant | Exon 1 of 10 | ENSP00000510794.2 | |||||
SHANK3 | ENST00000414786.7 | n.187_213delTCCCCGGCGCGAGCGGCCCCGGCCCGG | non_coding_transcript_exon_variant | Exon 1 of 23 | 5 | |||||
SHANK3 | ENST00000673971.2 | n.-41_-15delTCCCCGGCGCGAGCGGCCCCGGCCCGG | non_coding_transcript_exon_variant | Exon 1 of 23 | ENSP00000501192.2 | |||||
SHANK3 | ENST00000673971.2 | n.-41_-15delTCCCCGGCGCGAGCGGCCCCGGCCCGG | 5_prime_UTR_variant | Exon 1 of 23 | ENSP00000501192.2 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD4 genome Cov.: 28
ClinVar
Submissions by phenotype
Phelan-McDermid syndrome Uncertain:1
The variant in the exon 3 causes a change in protein length as a result of an in-frame deletion/insertion at nucleotide position 182 to 211. This change causes a deletion of the amino acid phenylalanine at position 62 to glycine at position 71 and an insertion of a cysteine. This variant is classified as very rare since it is absent in gnomAD v4.1.0. Segregation of the parents revealed a de novo occurrence in the patient. In summary, the variant is classified as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.