Variant 11-126445054-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_032531.4(KIRREL3):c.1177G>A(p.Ala393Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,614,008 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

KIRREL3
NM_032531.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38826638).

BP6

Variant 11-126445054-C-T is Benign according to our data. Variant chr11-126445054-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 129421.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-126445054-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	10/17	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.1177G>A	p.Ala393Thr	missense_variant	10/17	1	NM_032531.4	ENSP00000435466.2	Q8IZU9-1
KIRREL3	ENST00000529097.6 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	10/16	1		ENSP00000434081.2	E9PRX9
KIRREL3	ENST00000525704.2 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	10/14	1		ENSP00000435094.2	Q8IZU9-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249112

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000105

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000570

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 16, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

L;.;L

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.050

D;T;D

Sift4G

Uncertain

0.049

D;D;D

Polyphen

1.0

D;P;D

Vest4

0.60

MutPred

0.31

Gain of phosphorylation at A393 (P = 0.0884);Gain of phosphorylation at A393 (P = 0.0884);Gain of phosphorylation at A393 (P = 0.0884);

MVP

0.29

MPC

1.2

ClinPred

0.38

GERP RS

5.3

Varity_R

0.44

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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