Variant chr11-126424922-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032531.4(KIRREL3):c.1995C>T(p.Gly665Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.636 in 1,604,440 control chromosomes in the GnomAD database, including 327,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34316 hom., cov: 35)

Exomes 𝑓: 0.63 ( 293120 hom. )

Consequence

KIRREL3
NM_032531.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 11-126424922-G-A is Benign according to our data. Variant chr11-126424922-G-A is described in ClinVar as [Benign]. Clinvar id is 129425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126424922-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4 linkuse as main transcript	c.1995C>T	p.Gly665Gly	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.1995C>T	p.Gly665Gly	synonymous_variant	17/17	1	NM_032531.4	ENSP00000435466.2	Q8IZU9-1
KIRREL3	ENST00000529097.6 linkuse as main transcript	c.1959C>T	p.Gly653Gly	synonymous_variant	16/16	1		ENSP00000434081.2	E9PRX9
ST3GAL4	ENST00000524834.5 linkuse as main transcript	n.630-15264G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101646

AN:

152066

Hom.:

34299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.649

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.661

AC:

162630

AN:

245874

Hom.:

54549

AF XY:

0.660

AC XY:

88068

AN XY:

133458

show subpopulations

Gnomad AFR exome

AF:

0.720

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.908

Gnomad SAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.633

Gnomad OTH exome

AF:

0.664

GnomAD4 exome

AF:

0.633

AC:

919027

AN:

1452256

Hom.:

293120

Cov.:

AF XY:

0.634

AC XY:

456527

AN XY:

720542

show subpopulations

Gnomad4 AFR exome

AF:

0.724

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.776

Gnomad4 EAS exome

AF:

0.889

Gnomad4 SAS exome

AF:

0.647

Gnomad4 FIN exome

AF:

0.645

Gnomad4 NFE exome

AF:

0.616

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.668

AC:

101714

AN:

152184

Hom.:

34316

Cov.:

AF XY:

0.671

AC XY:

49937

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.719

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.781

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.649

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.629

Gnomad4 OTH

AF:

0.678

Alfa

AF:

0.650

Hom.:

18185

Bravo

AF:

0.668

Asia WGS

AF:

0.730

AC:

2539

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2019	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.7

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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