NM_032531.4:c.55+5957C>T

Variant names:

• chr11-126994498-G-A
• rs488054
• NM_032531.4:c.55+5957C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032531.4(KIRREL3):​c.55+5957C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00020 (0 hom., cov: 32)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 2 publications found

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: AD, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000255317 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BS2: High AC in GnomAd4 at 30 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	NM_032531.4	MANE Select	c.55+5957C>T		intron	N/A	NP_115920.1	Q8IZU9-1
	KIRREL3	NM_001441252.1		c.55+5957C>T		intron	N/A	NP_001428181.1
	KIRREL3	NM_001441253.1		c.55+5957C>T		intron	N/A	NP_001428182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	ENST00000525144.7	TSL:1 MANE Select	c.55+5957C>T		intron	N/A	ENSP00000435466.2	Q8IZU9-1
	KIRREL3	ENST00000529097.6	TSL:1	c.55+5957C>T		intron	N/A	ENSP00000434081.2	E9PRX9
	KIRREL3	ENST00000525704.2	TSL:1	c.55+5957C>T		intron	N/A	ENSP00000435094.2	Q8IZU9-2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74428

African (AFR) AF: 0.000169 AC: 7 AN: 41480

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		1.7

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

Other links and lift over

dbSNP: rs488054; hg19: chr11-126864394;