Variant chr22-26169713-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021115.5(SEZ6L):c.44C>G(p.Ser15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,301,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SEZ6L
NM_021115.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.153

Variant links:

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]

SEZ6L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09816906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5 linkuse as main transcript	c.44C>G	p.Ser15Trp	missense_variant	1/17	ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11 linkuse as main transcript	c.44C>G	p.Ser15Trp	missense_variant	1/17	1	NM_021115.5	P4	Q9BYH1-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1149262

Hom.:

Cov.:

AF XY:

0.00000902

AC XY:

AN XY:

554250

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000407

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000216

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.44C>G (p.S15W) alteration is located in exon 1 (coding exon 1) of the SEZ6L gene. This alteration results from a C to G substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.74

T;T;T;T;T;T

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.098

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;N;N;N;N

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.88

N;N;N;.;N;N

REVEL

Benign

0.097

Sift

Uncertain

0.0020

D;D;D;.;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D

Polyphen

0.98, 0.99

.;D;D;.;D;D

Vest4

0.45

MutPred

0.42

Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);

MVP

0.068

MPC

0.14

ClinPred

0.81

GERP RS

3.7

Varity_R

0.21

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over