11-126440261-G-A

Position:

• chr11-126440261-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032531.4(KIRREL3):​c.1353+188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 709,014 control chromosomes in the GnomAD database, including 27,661 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8289 hom., cov: 33)
  • Exomes 𝑓: 0.25 (19372 hom.)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.1353+188C>T		intron_variant		ENST00000525144.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.1353+188C>T		intron_variant		1	NM_032531.4	P4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47665 AN: 151992 Hom.: 8269 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.335

GnomAD3 exomes AF: 0.244 AC: 33582 AN: 137726 Hom.: 4581 AF XY: 0.240 AC XY: 17967 AN XY: 74802

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.254 AC: 141435 AN: 556904 Hom.: 19372 Cov.: 5 AF XY: 0.249 AC XY: 74931 AN XY: 301166

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.314 AC: 47727 AN: 152110 Hom.: 8289 Cov.: 33 AF XY: 0.306 AC XY: 22724 AN XY: 74382

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.333

Alfa AF: 0.282 Hom.: 8977

Bravo AF: 0.327

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3740918; hg19: chr11-126310156; COSMIC: COSV69383732;