11-126423390-A-T

Position:

• chr11-126423390-A-T

Variant summary

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

The NM_032531.4(KIRREL3):​c.*1190T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,956 control chromosomes in the GnomAD database, including 25,842 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 0.58 (25841 hom., cov: 32)
  • Exomes 𝑓: 0.42 (1 hom.)
• Consequence: KIRREL3 NM_032531.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.*1190T>A		3_prime_UTR_variant	17/17	ENST00000525144.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.*1190T>A		3_prime_UTR_variant	17/17	1	NM_032531.4	P4
ST3GAL4	ENST00000524834.5	n.629+13979A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87568 AN: 151822 Hom.: 25798 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.417 AC: 5 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.577 AC: 87671 AN: 151944 Hom.: 25841 Cov.: 32 AF XY: 0.576 AC XY: 42795 AN XY: 74254

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.579

Alfa AF: 0.443 Hom.: 1283

Bravo AF: 0.589

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.77
DANN	Benign	0.78

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: rs752805; hg19: chr11-126293285;