rs779140644
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000262795.7(SHANK3):c.-312G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,525,648 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0035 ( 14 hom. )
Consequence
SHANK3
ENST00000262795.7 5_prime_UTR
ENST00000262795.7 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.46
Genes affected
SHANK3 (HGNC:14294): (SH3 and multiple ankyrin repeat domains 3) This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD), which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene also cause schizophrenia type 15, and are a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq, Mar 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 22-50675030-G-A is Benign according to our data. Variant chr22-50675030-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0022 (334/151568) while in subpopulation AMR AF= 0.00439 (67/15266). AF 95% confidence interval is 0.00355. There are 1 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 334 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHANK3 | NM_001372044.2 | c.289-18G>A | intron_variant | ENST00000710353.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHANK3 | ENST00000262795.7 | c.-312G>A | 5_prime_UTR_variant | 1/22 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00221 AC: 334AN: 151454Hom.: 1 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
334
AN:
151454
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00229 AC: 288AN: 125692Hom.: 0 AF XY: 0.00226 AC XY: 156AN XY: 68930
GnomAD3 exomes
AF:
AC:
288
AN:
125692
Hom.:
AF XY:
AC XY:
156
AN XY:
68930
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00354 AC: 4858AN: 1374080Hom.: 14 Cov.: 31 AF XY: 0.00334 AC XY: 2260AN XY: 676782
GnomAD4 exome
AF:
AC:
4858
AN:
1374080
Hom.:
Cov.:
31
AF XY:
AC XY:
2260
AN XY:
676782
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00220 AC: 334AN: 151568Hom.: 1 Cov.: 31 AF XY: 0.00201 AC XY: 149AN XY: 74058
GnomAD4 genome
?
AF:
AC:
334
AN:
151568
Hom.:
Cov.:
31
AF XY:
AC XY:
149
AN XY:
74058
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 14, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at