NM_021115.5:c.1348+2060T>C

Variant names:

• chr22-26301229-T-C
• rs591044
• NM_021115.5:c.1348+2060T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.99).
• 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 rank	MANE	Protein	UniProt
SEZ6L	NM_021115.5	c.1348+2060T>C		intron_variant	Intron 5 of 16	ENST00000248933.11	NP_066938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L	ENST00000248933.11	c.1348+2060T>C		intron_variant	Intron 5 of 16	1	NM_021115.5	ENSP00000248933.6

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

African (AFR) AF: 0.625 AC: 25956 AN: 41502

American (AMR) AF: 0.360 AC: 5511 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3470

East Asian (EAS) AF: 0.111 AC: 573 AN: 5178

South Asian (SAS) AF: 0.181 AC: 874 AN: 4828

European-Finnish (FIN) AF: 0.382 AC: 4047 AN: 10582

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29493 AN: 67852

Other (OTH) AF: 0.446 AC: 943 AN: 2114

Alfa AF: 0.438 Hom.: 40697

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
PhyloP100		-1.3
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: rs591044; hg19: chr22-26697195;