Variant rs2341009 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001372044.2(SHANK3):c.1527+106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,332,436 control chromosomes in the GnomAD database, including 365,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 43962 hom., cov: 31)

Exomes 𝑓: 0.74 ( 321306 hom. )

Consequence

SHANK3
NM_001372044.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-50695152-C-A is Benign according to our data. Variant chr22-50695152-C-A is described in ClinVar as [Benign]. Clinvar id is 1228812.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHANK3	NM_001372044.2 linkuse as main transcript	c.1527+106C>A		intron_variant		ENST00000710353.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris
SHANK3	ENST00000262795.7 linkuse as main transcript	c.947+104C>A	intron_variant	5	P1
SHANK3	ENST00000673971.2 linkuse as main transcript	c.1304+104C>A	intron_variant, NMD_transcript_variant
SHANK3	ENST00000414786.7 linkuse as main transcript	n.1531+104C>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115331

AN:

151878

Hom.:

43932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.780

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.736

AC:

868411

AN:

1180440

Hom.:

321306

AF XY:

0.733

AC XY:

423302

AN XY:

577876

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.840

Gnomad4 ASJ exome

AF:

0.784

Gnomad4 EAS exome

AF:

0.715

Gnomad4 SAS exome

AF:

0.665

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.732

Gnomad4 OTH exome

AF:

0.739

GnomAD4 genome

AF:

0.759

AC:

115415

AN:

151996

Hom.:

43962

Cov.:

AF XY:

0.759

AC XY:

56380

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.815

Gnomad4 ASJ

AF:

0.780

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.800

Gnomad4 NFE

AF:

0.734

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.740

Hom.:

39865

Bravo

AF:

0.763

Asia WGS

AF:

0.656

AC:

2281

AN:

3478

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

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.59

DANN

Benign

0.79

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.

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