chr11-126424766-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_032531.4(KIRREL3):c.2151C>T(p.Ser717=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,032 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.010 ( 26 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 25 hom. )
Consequence
KIRREL3
NM_032531.4 synonymous
NM_032531.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.16
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 11-126424766-G-A is Benign according to our data. Variant chr11-126424766-G-A is described in ClinVar as [Benign]. Clinvar id is 129426.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=3.16 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1535/152338) while in subpopulation AFR AF= 0.0347 (1443/41568). AF 95% confidence interval is 0.0332. There are 26 homozygotes in gnomad4. There are 721 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1537 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.2151C>T | p.Ser717= | synonymous_variant | 17/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.2151C>T | p.Ser717= | synonymous_variant | 17/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.2115C>T | p.Ser705= | synonymous_variant | 16/16 | 1 | A1 | ||
ST3GAL4 | ENST00000524834.5 | n.629+15355G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0101 AC: 1537AN: 152220Hom.: 26 Cov.: 33
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GnomAD3 exomes AF: 0.00268 AC: 668AN: 249180Hom.: 11 AF XY: 0.00205 AC XY: 277AN XY: 135182
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GnomAD4 exome AF: 0.00110 AC: 1603AN: 1461694Hom.: 25 Cov.: 31 AF XY: 0.000920 AC XY: 669AN XY: 727128
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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 | 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