Variant 11-126424934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032531.4(KIRREL3):c.1983G>A(p.Leu661Leu) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.179

Variant links:

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]

KIRREL3 links:

ST3GAL4 (HGNC:):

ST3GAL4 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4 linkuse as main transcript	c.1983G>A	p.Leu661Leu	synonymous_variant	17/17	ENST00000525144.7	NP_115920.1	Q8IZU9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIRREL3	ENST00000525144.7 linkuse as main transcript	c.1983G>A	p.Leu661Leu	synonymous_variant	17/17	1	NM_032531.4	ENSP00000435466.2	Q8IZU9-1
KIRREL3	ENST00000529097.6 linkuse as main transcript	c.1947G>A	p.Leu649Leu	synonymous_variant	16/16	1		ENSP00000434081.2	E9PRX9
ST3GAL4	ENST00000524834.5 linkuse as main transcript	n.630-15252C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

331

AN:

152214

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00236

AC XY:

312

AN XY:

132088

show subpopulations

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.:

Cov.:

AF XY:

0.00264

AC XY:

1897

AN XY:

718492

show subpopulations

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.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74490

show subpopulations

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.:

Bravo

AF:

0.00191

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	KIRREL3: BP4, BP7 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over