rs591044

Positions:

• chr22-26301229-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021115.5(SEZ6L):​c.1348+2060T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,014 control chromosomes in the GnomAD database, including 17,222 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 0.46 (17222 hom., cov: 33)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.1348+2060T>C		intron_variant		ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.1348+2060T>C		intron_variant		1	NM_021115.5	ENSP00000248933	P4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69514 AN: 151894 Hom.: 17199 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.458 AC: 69587 AN: 152014 Hom.: 17222 Cov.: 33 AF XY: 0.448 AC XY: 33300 AN XY: 74302

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.446

Alfa AF: 0.428 Hom.: 25455

Bravo AF: 0.468

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.49

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: rs591044; hg19: chr22-26697195;