chr11-126424799-A-C
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_032531.4(KIRREL3):āc.2118T>Gā(p.Leu706=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,614,004 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0045 ( 10 hom., cov: 33)
Exomes š: 0.00045 ( 3 hom. )
Consequence
KIRREL3
NM_032531.4 synonymous
NM_032531.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.609
Genes affected
KIRREL3 (HGNC:23204): (kirre like nephrin family adhesion molecule 3) The protein encoded by this gene is a member of the nephrin-like protein family. These proteins are expressed in fetal and adult brain, and also in podocytes of kidney glomeruli. The cytoplasmic domains of these proteins interact with the C-terminus of podocin, also expressed in the podocytes, cells involved in ensuring size- and charge-selective ultrafiltration. The protein encoded by this gene is a synaptic cell adhesion molecule with multiple extracellular immunoglobulin-like domains and a cytoplasmic PDZ domain-binding motif. Mutations in this gene are associated with several neurological and cognitive disorders. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 11-126424799-A-C is Benign according to our data. Variant chr11-126424799-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 725838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.609 with no splicing effect.
BS2
High AC in GnomAd4 at 681 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.2118T>G | p.Leu706= | synonymous_variant | 17/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.2118T>G | p.Leu706= | synonymous_variant | 17/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.2082T>G | p.Leu694= | synonymous_variant | 16/16 | 1 | A1 | ||
ST3GAL4 | ENST00000524834.5 | n.630-15387A>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00447 AC: 680AN: 152188Hom.: 10 Cov.: 33
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GnomAD3 exomes AF: 0.00123 AC: 306AN: 249212Hom.: 2 AF XY: 0.000917 AC XY: 124AN XY: 135212
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GnomAD4 exome AF: 0.000447 AC: 653AN: 1461698Hom.: 3 Cov.: 31 AF XY: 0.000367 AC XY: 267AN XY: 727134
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GnomAD4 genome AF: 0.00447 AC: 681AN: 152306Hom.: 10 Cov.: 33 AF XY: 0.00426 AC XY: 317AN XY: 74482
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KIRREL3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 07, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at