22-26374424-A-G

Position:

• chr22-26374424-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.2827+941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,816 control chromosomes in the GnomAD database, including 19,074 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 0.48 (19074 hom., cov: 30)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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 = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.2827+941A>G		intron_variant		ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.2827+941A>G		intron_variant		1	NM_021115.5	P4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73492 AN: 151698 Hom.: 19048 Cov.: 30

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.485 AC: 73572 AN: 151816 Hom.: 19074 Cov.: 30 AF XY: 0.495 AC XY: 36706 AN XY: 74194

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.457

Alfa AF: 0.478 Hom.: 22839

Bravo AF: 0.481

Asia WGS AF: 0.779 AC: 2705 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	0.66
DANN	Benign	0.75

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: rs731276; hg19: chr22-26770390;