NM_021115.5:c.835+523C>T

Variant names:

• chr22-26293669-C-T
• rs688034
• NM_021115.5:c.835+523C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021115.5(SEZ6L):​c.835+523C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,126 control chromosomes in the GnomAD database, including 5,129 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 0.23 (5129 hom., cov: 32)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 20 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	NM_021115.5	MANE Select	c.835+523C>T		intron	N/A	NP_066938.2
	SEZ6L	NM_001184773.2		c.835+523C>T		intron	N/A	NP_001171702.1
	SEZ6L	NM_001184774.2		c.835+523C>T		intron	N/A	NP_001171703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	ENST00000248933.11	TSL:1 MANE Select	c.835+523C>T		intron	N/A	ENSP00000248933.6
	SEZ6L	ENST00000404234.7	TSL:1	c.835+523C>T		intron	N/A	ENSP00000384772.3
	SEZ6L	ENST00000629590.2	TSL:1	c.835+523C>T		intron	N/A	ENSP00000485720.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35427 AN: 152008 Hom.: 5131 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.233 AC: 35413 AN: 152126 Hom.: 5129 Cov.: 32 AF XY: 0.228 AC XY: 16987 AN XY: 74366

African (AFR) AF: 0.107 AC: 4427 AN: 41500

American (AMR) AF: 0.196 AC: 2997 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.109 AC: 524 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2770 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22459 AN: 67980

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.292 Hom.: 13062

Bravo AF: 0.223

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		-1.2
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: rs688034; hg19: chr22-26689635;