22-26244883-A-G

Variant names:

• chr22-26244883-A-G
• rs1207405
• NM_021115.5:c.95-47523A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.95-47523A>G		intron_variant	Intron 1 of 16	ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.95-47523A>G		intron_variant	Intron 1 of 16	1	NM_021115.5	ENSP00000248933.6

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

African (AFR) AF: 0.805 AC: 33398 AN: 41488

American (AMR) AF: 0.773 AC: 11812 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3195 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3835 AN: 5156

South Asian (SAS) AF: 0.805 AC: 3872 AN: 4812

European-Finnish (FIN) AF: 0.912 AC: 9672 AN: 10600

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62904 AN: 68004

Other (OTH) AF: 0.866 AC: 1829 AN: 2112

Alfa AF: 0.907 Hom.: 103189

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
PhyloP100		-1.4
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: rs1207405; hg19: chr22-26640849;