rs17299838

Positions:

• chr22-26182255-C-G
• chr22-26182255-C-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+12492C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,278 control chromosomes in the GnomAD database, including 475 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 0.070 (475 hom., cov: 32)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.94+12492C>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.94+12492C>G		intron_variant		1	NM_021115.5	ENSP00000248933.6

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10702 AN: 152160 Hom.: 475 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0703 AC: 10704 AN: 152278 Hom.: 475 Cov.: 32 AF XY: 0.0651 AC XY: 4851 AN XY: 74476

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0586

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0425 Hom.: 42

Bravo AF: 0.0670

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0040
DANN	Benign	0.48

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: rs17299838; hg19: chr22-26578221;