chr11-126424934-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_032531.4(KIRREL3):c.1983G>A(p.Leu661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,601,340 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 9 hom. )
Consequence
KIRREL3
NM_032531.4 synonymous
NM_032531.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.179
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 11-126424934-C-T is Benign according to our data. Variant chr11-126424934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 211304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.179 with no splicing effect.
BS2
?
High AC in GnomAd at 331 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.1983G>A | p.Leu661= | synonymous_variant | 17/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.1983G>A | p.Leu661= | synonymous_variant | 17/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.1947G>A | p.Leu649= | synonymous_variant | 16/16 | 1 | A1 | ||
ST3GAL4 | ENST00000524834.5 | n.630-15252C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00217 AC: 331AN: 152214Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00231 AC: 562AN: 243318Hom.: 1 AF XY: 0.00236 AC XY: 312AN XY: 132088
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GnomAD4 exome AF: 0.00275 AC: 3985AN: 1449008Hom.: 9 Cov.: 34 AF XY: 0.00264 AC XY: 1897AN XY: 718492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | KIRREL3: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 20, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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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