3-12154402-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_003256.4(TIMP4):c.402C>T(p.Ile134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
TIMP4
NM_003256.4 synonymous
NM_003256.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.262
Genes affected
TIMP4 (HGNC:11823): (TIMP metallopeptidase inhibitor 4) 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. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008]
SYN2 (HGNC:11495): (synapsin II) 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. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Polymorphisms in this gene are associated with abnormal presynaptic function and related neuronal disorders, including autism, epilepsy, bipolar disorder and schizophrenia. Alternative splicing of this gene results in multiple transcript variants. The tissue inhibitor of metalloproteinase 4 gene is located within an intron of this gene and is transcribed in the opposite direction. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 3-12154402-G-A is Benign according to our data. Variant chr3-12154402-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 745640.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.262 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMP4 | NM_003256.4 | c.402C>T | p.Ile134= | synonymous_variant | 4/5 | ENST00000287814.5 | |
SYN2 | NM_133625.6 | c.774+3076G>A | intron_variant | ENST00000621198.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMP4 | ENST00000287814.5 | c.402C>T | p.Ile134= | synonymous_variant | 4/5 | 1 | NM_003256.4 | P1 | |
SYN2 | ENST00000621198.5 | c.774+3076G>A | intron_variant | 1 | NM_133625.6 | P2 | |||
SYN2 | ENST00000620175.4 | c.774+3076G>A | intron_variant | 1 | A2 | ||||
SYN2 | ENST00000439861.5 | n.225+3076G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251478Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135912
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727244
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 21, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at