rs375855596

chr11-126424934-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_032531.4(KIRREL3):c.1983G>A(p.Leu661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,601,340 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (9 hom.)
• Consequence: KIRREL3 NM_032531.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.179

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-126424934-C-T is Benign according to our data. Variant chr11-126424934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 211304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.179 with no splicing effect.
• BS2: High AC in GnomAd at 331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.1983G>A	p.Leu661=	synonymous_variant	17/17	ENST00000525144.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.1983G>A	p.Leu661=	synonymous_variant	17/17	1	NM_032531.4	P4
KIRREL3	ENST00000529097.6	c.1947G>A	p.Leu649=	synonymous_variant	16/16	1		A1
ST3GAL4	ENST00000524834.5	n.630-15252C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 331 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00231 AC: 562 AN: 243318 Hom.: 1 AF XY: 0.00236 AC XY: 312 AN XY: 132088

Gnomad AFR exome AF: 0.000265

Gnomad AMR exome AF: 0.000616

Gnomad ASJ exome AF: 0.00127

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00148

Gnomad FIN exome AF: 0.00607

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.00271

GnomAD4 exome AF: 0.00275 AC: 3985 AN: 1449008 Hom.: 9 Cov.: 34 AF XY: 0.00264 AC XY: 1897 AN XY: 718492

Gnomad4 AFR exome AF: 0.000362

Gnomad4 AMR exome AF: 0.000543

Gnomad4 ASJ exome AF: 0.00152

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00696

Gnomad4 NFE exome AF: 0.00297

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.00217 AC: 331 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00254 AC XY: 189 AN XY: 74490

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00271 Hom.: 0

Bravo AF: 0.00191

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	KIRREL3: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	8.9
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375855596; hg19: chr11-126294829;