22-26257396-C-G

Position:

• chr22-26257396-C-G

Variant summary

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

The NM_021115.5(SEZ6L):​c.95-35010C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,970 control chromosomes in the GnomAD database, including 29,812 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 0.62 (29812 hom., cov: 32)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.95-35010C>G		intron_variant		ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.95-35010C>G		intron_variant		1	NM_021115.5	ENSP00000248933	P4

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93676 AN: 151852 Hom.: 29784 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.617 AC: 93749 AN: 151970 Hom.: 29812 Cov.: 32 AF XY: 0.621 AC XY: 46123 AN XY: 74306

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.633

Alfa AF: 0.620 Hom.: 3698

Bravo AF: 0.616

Asia WGS AF: 0.838 AC: 2913 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.33

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: rs1207393; hg19: chr22-26653362;