NM_021115.5:c.2212+3489C>G

Variant names:

• chr22-26344121-C-G
• rs5752309
• NM_021115.5:c.2212+3489C>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.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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.2212+3489C>G		intron_variant	Intron 10 of 16	ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.2212+3489C>G		intron_variant	Intron 10 of 16	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

African (AFR) AF: 0.132 AC: 5472 AN: 41482

American (AMR) AF: 0.186 AC: 2841 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1680 AN: 5158

South Asian (SAS) AF: 0.364 AC: 1756 AN: 4818

European-Finnish (FIN) AF: 0.261 AC: 2766 AN: 10588

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12306 AN: 67988

Other (OTH) AF: 0.207 AC: 437 AN: 2110

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
PhyloP100		0.089
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: rs5752309; hg19: chr22-26740087;