NM_001372044.2:c.1798+1947C>T

Variant names:

• chr22-50700750-C-T
• rs736334
• NM_001372044.2:c.1798+1947C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50700750-C-T
• chrNW_015148969.2-36910-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372044.2(SHANK3):​c.1798+1947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,072 control chromosomes in the GnomAD database, including 6,489 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 0.28 (6489 hom., cov: 33)
• Consequence: SHANK3 NM_001372044.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Phelan-McDermid syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• schizophrenia 15

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372044.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHANK3	NM_001372044.2	MANE Select	c.1798+1947C>T		intron	N/A	NP_001358973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHANK3	ENST00000692848.2		c.1795+1947C>T		intron	N/A	ENSP00000510794.2
	SHANK3	ENST00000262795.8	TSL:5	c.1213+1947C>T		intron	N/A	ENSP00000489147.3
	SHANK3	ENST00000414786.8	TSL:5	n.1797+1947C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42409 AN: 151952 Hom.: 6470 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42476 AN: 152072 Hom.: 6489 Cov.: 33 AF XY: 0.286 AC XY: 21274 AN XY: 74326

African (AFR) AF: 0.355 AC: 14730 AN: 41484

American (AMR) AF: 0.370 AC: 5656 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.346 AC: 1783 AN: 5148

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4816

European-Finnish (FIN) AF: 0.355 AC: 3753 AN: 10570

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14343 AN: 67976

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.216 Hom.: 5323

Bravo AF: 0.283

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs736334; hg19: chr22-51139178; COSMIC: COSV53191513;