Variant 22-50674428-G-GCGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2

The NM_001372044.2(SHANK3):c.37_39dup(p.Ala13dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 6 hom., cov: 20)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

SHANK3
NM_001372044.2 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

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 -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001372044.2

BP6

Variant 22-50674428-G-GCGC is Benign according to our data. Variant chr22-50674428-G-GCGC is described in ClinVar as [Benign]. Clinvar id is 3026192.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00301 (396/131666) while in subpopulation AFR AF= 0.00904 (324/35828). AF 95% confidence interval is 0.00823. There are 6 homozygotes in gnomad4. There are 191 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High AC in GnomAd4 at 396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK3	NM_001372044.2 linkuse as main transcript	c.37_39dup	p.Ala13dup	inframe_insertion	2/25	ENST00000710353.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
SHANK3	ENST00000692848.1 linkuse as main transcript	c.-191_-189dup	5_prime_UTR_variant	1/10
SHANK3	ENST00000414786.7 linkuse as main transcript	n.37_39dup	non_coding_transcript_exon_variant	1/23	5
SHANK3	ENST00000673971.2 linkuse as main transcript	c.-191_-189dup	5_prime_UTR_variant, NMD_transcript_variant	1/23

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

395

AN:

131642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00903

Gnomad AMI

AF:

0.0288

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000486

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000443

Gnomad OTH

AF:

0.00221

GnomAD4 exome

AF:

0.000360

AC:

AN:

11126

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

8220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00231

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000340

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00301

AC:

396

AN:

131666

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

191

AN XY:

63670

show subpopulations

Gnomad4 AFR

AF:

0.00904

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000488

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000273

Gnomad4 NFE

AF:

0.000443

Gnomad4 OTH

AF:

0.00219

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

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

SHANK3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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