rs1001469

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372044.2(SHANK3):​c.1798+1522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 151,798 control chromosomes in the GnomAD database, including 48,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48414 hom., cov: 29)

Consequence

SHANK3
NM_001372044.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SHANK3NM_001372044.2 linkuse as main transcriptc.1798+1522A>G intron_variant ENST00000710353.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SHANK3ENST00000262795.7 linkuse as main transcriptc.1213+1522A>G intron_variant 5 P1

Frequencies

GnomAD3 genomes
AF:
0.798
AC:
121033
AN:
151680
Hom.:
48396
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.790
Gnomad AMI
AF:
0.829
Gnomad AMR
AF:
0.842
Gnomad ASJ
AF:
0.823
Gnomad EAS
AF:
0.644
Gnomad SAS
AF:
0.772
Gnomad FIN
AF:
0.832
Gnomad MID
AF:
0.791
Gnomad NFE
AF:
0.799
Gnomad OTH
AF:
0.795
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.798
AC:
121102
AN:
151798
Hom.:
48414
Cov.:
29
AF XY:
0.798
AC XY:
59138
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.790
Gnomad4 AMR
AF:
0.842
Gnomad4 ASJ
AF:
0.823
Gnomad4 EAS
AF:
0.644
Gnomad4 SAS
AF:
0.772
Gnomad4 FIN
AF:
0.832
Gnomad4 NFE
AF:
0.799
Gnomad4 OTH
AF:
0.788
Alfa
AF:
0.798
Hom.:
17360
Bravo
AF:
0.797
Asia WGS
AF:
0.698
AC:
2429
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
7.5
DANN
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1001469; hg19: chr22-51138753; API