rs201725914

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_032531.4(KIRREL3):c.908T>C(p.Val303Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00089 in 1,613,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 0 hom. )

Consequence

KIRREL3
NM_032531.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:2B:2

Conservation

PhyloP100: 4.10

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, autosomal dominant 4
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KIRREL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12330669).

BP6

Variant 11-126449098-A-G is Benign according to our data. Variant chr11-126449098-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 129429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 81 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIRREL3	NM_032531.4 link	c.908T>C	p.Val303Ala	missense_variant	Exon 8 of 17	ENST00000525144.7	NP_115920.1	Q8IZU9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIRREL3	ENST00000525144.7 link	c.908T>C	p.Val303Ala	missense_variant	Exon 8 of 17	1	NM_032531.4	ENSP00000435466.2	Q8IZU9-1
KIRREL3	ENST00000529097.6 link	c.908T>C	p.Val303Ala	missense_variant	Exon 8 of 16	1		ENSP00000434081.2	E9PRX9
KIRREL3	ENST00000525704.2 link	c.908T>C	p.Val303Ala	missense_variant	Exon 8 of 14	1		ENSP00000435094.2	Q8IZU9-2

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000421

AC:

105

AN:

249232

AF XY:

0.000481

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000752

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000927

AC:

1355

AN:

1461636

Hom.:

Cov.:

AF XY:

0.000924

AC XY:

672

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00115

AC:

1281

AN:

1111820

Other (OTH)

AF:

0.000514

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000533

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

67974

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000871

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000238

AC:

ESP6500EA

AF:

0.000593

AC:

ExAC

AF:

0.000306

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

May 29, 2014

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

L;.;L

PhyloP100

4.1

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.94

P;D;D

Vest4

0.32

MVP

0.31

MPC

1.4

ClinPred

0.049

GERP RS

5.3

Varity_R

0.11

gMVP

0.68

Mutation Taster

=18/82

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs201725914

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over