rs200243864
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_032531.4(KIRREL3):c.870C>A(p.Ile290=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 1,613,968 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00098 ( 7 hom. )
Consequence
KIRREL3
NM_032531.4 synonymous
NM_032531.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.403
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]
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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=-0.43).
BP6
?
Variant 11-126449136-G-T is Benign according to our data. Variant chr11-126449136-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 211308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.403 with no splicing effect.
BS2
?
High AC in GnomAd4 at 89 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.870C>A | p.Ile290= | synonymous_variant | 8/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.870C>A | p.Ile290= | synonymous_variant | 8/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.870C>A | p.Ile290= | synonymous_variant | 8/16 | 1 | A1 | ||
KIRREL3 | ENST00000525704.2 | c.870C>A | p.Ile290= | synonymous_variant | 8/14 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000591 AC: 90AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000843 AC: 210AN: 249122Hom.: 2 AF XY: 0.000969 AC XY: 131AN XY: 135130
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GnomAD4 exome AF: 0.000980 AC: 1432AN: 1461630Hom.: 7 Cov.: 31 AF XY: 0.00101 AC XY: 737AN XY: 727096
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GnomAD4 genome ? AF: 0.000584 AC: 89AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000618 AC XY: 46AN XY: 74490
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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
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 26, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | KIRREL3: BP4, BP7 - |
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