chr11-126424857-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_032531.4(KIRREL3):c.2060G>A(p.Arg687His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
KIRREL3
NM_032531.4 missense
NM_032531.4 missense
Scores
5
3
11
Clinical Significance
Conservation
PhyloP100: 7.33
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIRREL3 | NM_032531.4 | c.2060G>A | p.Arg687His | missense_variant | 17/17 | ENST00000525144.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIRREL3 | ENST00000525144.7 | c.2060G>A | p.Arg687His | missense_variant | 17/17 | 1 | NM_032531.4 | P4 | |
KIRREL3 | ENST00000529097.6 | c.2024G>A | p.Arg675His | missense_variant | 16/16 | 1 | A1 | ||
ST3GAL4 | ENST00000524834.5 | n.630-15329C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152238Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248818Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135096
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461556Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727048
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.2060G>A (p.R687H) alteration is located in exon 17 (coding exon 17) of the KIRREL3 gene. This alteration results from a G to A substitution at nucleotide position 2060, causing the arginine (R) at amino acid position 687 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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