chr22-26344121-C-G

Position:

• chr22-26344121-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.2212+3489C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,096 control chromosomes in the GnomAD database, including 2,880 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 0.19 (2880 hom., cov: 32)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.2212+3489C>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.2212+3489C>G		intron_variant		1	NM_021115.5	ENSP00000248933.6

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28249 AN: 151978 Hom.: 2880 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.186 AC: 28259 AN: 152096 Hom.: 2880 Cov.: 32 AF XY: 0.194 AC XY: 14429 AN XY: 74358

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0835 Hom.: 124

Bravo AF: 0.175

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.78

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: rs5752309; hg19: chr22-26740087;