rs713685

Positions:

• chr22-32812451-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000266085.7(TIMP3):​c.121+10329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,198 control chromosomes in the GnomAD database, including 546 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 0.076 (546 hom., cov: 32)
• Consequence: TIMP3 ENST00000266085.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

Genes affected

TIMP3 (HGNC:11822): (TIMP metallopeptidase inhibitor 3) This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM). Expression of this gene is induced in response to mitogenic stimulation and this netrin domain-containing protein is localized to the ECM. Mutations in this gene have been associated with the autosomal dominant disorder Sorsby's fundus dystrophy. [provided by RefSeq, Jul 2008]

SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

LOC124905104 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMP3	NM_000362.5	c.121+10329C>T		intron_variant		ENST00000266085.7	NP_000353.1
SYN3	NM_003490.4	c.711+52464G>A		intron_variant		ENST00000358763.7	NP_003481.3
LOC124905104	XR_007068068.1	n.1136C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP3	ENST00000266085.7	c.121+10329C>T		intron_variant		1	NM_000362.5	ENSP00000266085	P1
SYN3	ENST00000358763.7	c.711+52464G>A		intron_variant		5	NM_003490.4	ENSP00000351614	P1
SYN3	ENST00000462268.1	n.225+52464G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11600 AN: 152080 Hom.: 545 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0756

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

GnomAD4 genome AF: 0.0763 AC: 11611 AN: 152198 Hom.: 546 Cov.: 32 AF XY: 0.0745 AC XY: 5544 AN XY: 74396

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0868

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0952 Hom.: 244

Bravo AF: 0.0696

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.012
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs713685; hg19: chr22-33208437;