chr11-126424922-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_032531.4(KIRREL3):c.1995C>T(p.Gly665=) variant causes a synonymous change. The variant allele was found at a frequency of 0.636 in 1,604,440 control chromosomes in the GnomAD database, including 327,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.67 ( 34316 hom., cov: 35)
Exomes 𝑓: 0.63 ( 293120 hom. )
Consequence
KIRREL3
NM_032531.4 synonymous
NM_032531.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.21
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 11-126424922-G-A is Benign according to our data. Variant chr11-126424922-G-A is described in ClinVar as [Benign]. Clinvar id is 129425.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-126424922-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.1995C>T | p.Gly665= | synonymous_variant | 17/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.1995C>T | p.Gly665= | synonymous_variant | 17/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.1959C>T | p.Gly653= | synonymous_variant | 16/16 | 1 | A1 | ||
ST3GAL4 | ENST00000524834.5 | n.630-15264G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.668 AC: 101646AN: 152066Hom.: 34299 Cov.: 35
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GnomAD3 exomes AF: 0.661 AC: 162630AN: 245874Hom.: 54549 AF XY: 0.660 AC XY: 88068AN XY: 133458
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GnomAD4 exome AF: 0.633 AC: 919027AN: 1452256Hom.: 293120 Cov.: 64 AF XY: 0.634 AC XY: 456527AN XY: 720542
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at