22-26244883-A-G

Variant summary

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

The NM_021115.5(SEZ6L):c.95-47523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,132 control chromosomes in the GnomAD database, including 57,355 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 0.87 (57355 hom., cov: 31)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

SEZ6L-AS1 (HGNC:40521): (SEZ6L antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.95-47523A>G		intron_variant		ENST00000248933.11
SEZ6L-AS1	XR_002958742.2	n.1725T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.95-47523A>G		intron_variant		1	NM_021115.5	P4
SEZ6L-AS1	ENST00000414989.2	n.120-194T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131551 AN: 152014 Hom.: 57327 Cov.: 31

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.865 AC: 131638 AN: 152132 Hom.: 57355 Cov.: 31 AF XY: 0.860 AC XY: 63956 AN XY: 74348

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.866

Alfa AF: 0.913 Hom.: 81788

Bravo AF: 0.851

Asia WGS AF: 0.772 AC: 2686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.10
Dann	Benign	0.41

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: rs1207405; hg19: chr22-26640849;