rs5761405

chr22-26209677-A-Gchr22-26209677-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021115.5(SEZ6L):c.94+39914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 148,338 control chromosomes in the GnomAD database, including 575 homozygotes. 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 0.074 (575 hom., cov: 26)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

Genes affected

SEZ6L (HGNC:10763): (seizure related 6 homolog like) Predicted to act upstream of or within adult locomotory behavior; nervous system development; and regulation of protein kinase C signaling. Predicted to be located in endoplasmic reticulum and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.94+39914A>G		intron_variant		ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.94+39914A>G		intron_variant		1	NM_021115.5	P4

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 10893 AN: 148192 Hom.: 574 Cov.: 26

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0398

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0767

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

GnomAD4 genome AF: 0.0735 AC: 10909 AN: 148338 Hom.: 575 Cov.: 26 AF XY: 0.0776 AC XY: 5622 AN XY: 72468

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0278 Hom.: 8

Bravo AF: 0.0825

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.92

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

LitVar

Other links and lift over

dbSNP: rs5761405; hg19: chr22-26605643;