NM_032531.4:c.1995C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

16 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 -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.

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 rank	MANE	Protein	UniProt
KIRREL3	NM_032531.4 link	c.1995C>T	p.Gly665Gly	synonymous_variant	Exon 17 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.1995C>T	p.Gly665Gly	synonymous_variant	Exon 17 of 17	1	NM_032531.4	ENSP00000435466.2	Q8IZU9-1
KIRREL3	ENST00000529097.6 link	c.1959C>T	p.Gly653Gly	synonymous_variant	Exon 16 of 16	1		ENSP00000434081.2	E9PRX9
ST3GAL4	ENST00000524834.5 link	n.630-15264G>A		intron_variant	Intron 6 of 6	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

GnomAD2 exomes

AF:

0.661

AC:

162630

AN:

245874

AF XY:

0.660

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 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

African (AFR)

AF:

0.724

AC:

24054

AN:

33224

American (AMR)

AF:

0.590

AC:

26165

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

20114

AN:

25936

East Asian (EAS)

AF:

0.889

AC:

35077

AN:

39472

South Asian (SAS)

AF:

0.647

AC:

55663

AN:

85980

European-Finnish (FIN)

AF:

0.645

AC:

34242

AN:

53112

Middle Eastern (MID)

AF:

0.681

AC:

3909

AN:

5738

European-Non Finnish (NFE)

AF:

0.616

AC:

680936

AN:

1104542

Other (OTH)

AF:

0.648

AC:

38867

AN:

59942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

20756

41512

62268

83024

103780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.668

AC:

101714

AN:

152184

Hom.:

34316

Cov.:

AF XY:

0.671

AC XY:

49937

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.719

AC:

29859

AN:

41532

American (AMR)

AF:

0.627

AC:

9591

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2711

AN:

3470

East Asian (EAS)

AF:

0.906

AC:

4678

AN:

5166

South Asian (SAS)

AF:

0.649

AC:

3129

AN:

4824

European-Finnish (FIN)

AF:

0.647

AC:

6857

AN:

10592

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.629

AC:

42758

AN:

67986

Other (OTH)

AF:

0.678

AC:

1431

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1773

3546

5320

7093

8866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.654

Hom.:

23851

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

Jan 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.82

PhyloP100

4.2

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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NM_032531.4:c.1995C>T

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