11-126424569-G-A

Variant names:

• chr11-126424569-G-A
• rs3212318
• NM_032531.4:c.*11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032531.4(KIRREL3):​c.*11C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,612,698 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (209 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (192 hom.)
• Consequence: KIRREL3 NM_032531.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.58
• 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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-126424569-G-A is Benign according to our data. Variant chr11-126424569-G-A is described in ClinVar as [Benign]. Clinvar id is 1226507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIRREL3	NM_032531.4	c.*11C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000525144.7	NP_115920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIRREL3	ENST00000525144.7	c.*11C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_032531.4	ENSP00000435466.2
KIRREL3	ENST00000529097.6	c.*11C>T		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000434081.2
ST3GAL4	ENST00000524834.5	n.629+15158G>A		intron_variant	Intron 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4409 AN: 152230 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.00781 AC: 1942 AN: 248594 AF XY: 0.00591

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00693

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00464

GnomAD4 exome AF: 0.00311 AC: 4542 AN: 1460350 Hom.: 192 Cov.: 31 AF XY: 0.00261 AC XY: 1895 AN XY: 726338

African (AFR) AF: 0.107 AC: 3564 AN: 33432

American (AMR) AF: 0.00774 AC: 346 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00123 AC: 32 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00342 AC: 18 AN: 5260

European-Non Finnish (NFE) AF: 0.000181 AC: 201 AN: 1111300

Other (OTH) AF: 0.00591 AC: 356 AN: 60286

GnomAD4 genome AF: 0.0290 AC: 4417 AN: 152348 Hom.: 209 Cov.: 33 AF XY: 0.0274 AC XY: 2042 AN XY: 74508

African (AFR) AF: 0.0988 AC: 4109 AN: 41570

American (AMR) AF: 0.0135 AC: 207 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68028

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0144 Hom.: 38

Bravo AF: 0.0334

Asia WGS AF: 0.00491 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs3212318; hg19: chr11-126294464;