Variant summary

Our verdict is Benign. The variant received -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

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 links:

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]

ST3GAL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032531.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIRREL3	NM_032531.4	MANE Select	c.1983G>A	p.Leu661Leu	synonymous	Exon 17 of 17	NP_115920.1
KIRREL3	NM_001441252.1		c.2091G>A	p.Leu697Leu	synonymous	Exon 18 of 18	NP_001428181.1
KIRREL3	NM_001441253.1		c.2058G>A	p.Leu686Leu	synonymous	Exon 17 of 17	NP_001428182.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIRREL3	ENST00000525144.7	TSL:1 MANE Select	c.1983G>A	p.Leu661Leu	synonymous	Exon 17 of 17	ENSP00000435466.2
KIRREL3	ENST00000529097.6	TSL:1	c.1947G>A	p.Leu649Leu	synonymous	Exon 16 of 16	ENSP00000434081.2
ST3GAL4	ENST00000524834.5	TSL:2	n.630-15252C>T		intron	N/A

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

GnomAD2 exomes

AF:

0.00231

AC:

562

AN:

243318

AF XY:

0.00236

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 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

African (AFR)

AF:

0.000362

AC:

AN:

33174

American (AMR)

AF:

0.000543

AC:

AN:

44208

Ashkenazi Jewish (ASJ)

AF:

0.00152

AC:

AN:

25602

East Asian (EAS)

AF:

0.00

AC:

AN:

39404

South Asian (SAS)

AF:

0.00139

AC:

119

AN:

85440

European-Finnish (FIN)

AF:

0.00696

AC:

369

AN:

52982

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00297

AC:

3274

AN:

1102684

Other (OTH)

AF:

0.00229

AC:

137

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

257

513

770

1026

1283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152332

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41580

American (AMR)

AF:

0.00111

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00574

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00284

AC:

193

AN:

68028

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00271

Hom.:

Bravo

AF:

0.00191

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.9

(source)

DANN

Benign

0.84

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over