Variant 22-50674726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001372044.2(SHANK3):c.288+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,036,834 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00071 ( 3 hom. )

Consequence

SHANK3
NM_001372044.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.97

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]

SHANK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 22-50674726-C-T is Benign according to our data. Variant chr22-50674726-C-T is described in ClinVar as [Benign]. Clinvar id is 1271455.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHANK3	NM_001372044.2 linkuse as main transcript	c.288+22C>T		intron_variant		ENST00000710353.1	NP_001358973.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein
SHANK3	ENST00000692848.1 linkuse as main transcript	c.63+22C>T	intron_variant		ENSP00000510794
SHANK3	ENST00000673971.2 linkuse as main transcript	c.63+22C>T	intron_variant, NMD_transcript_variant		ENSP00000501192
SHANK3	ENST00000414786.7 linkuse as main transcript	n.290+22C>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

145290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000551

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000564

AC:

AN:

10638

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

6618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000710

AC:

633

AN:

891544

Hom.:

Cov.:

AF XY:

0.000728

AC XY:

307

AN XY:

421816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000377

Gnomad4 NFE exome

AF:

0.000785

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000296

AC:

AN:

145290

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

70714

show subpopulations

Gnomad4 AFR

AF:

0.0000992

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000116

Gnomad4 NFE

AF:

0.000551

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over