Genetic Variant SEZ6L2:p.Thr108Ile (chr16-29897010-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001243332.2(SEZ6L2):c.323C>T(p.Thr108Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000126 in 1,584,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SEZ6L2
NM_001243332.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.40

Publications

0 publications found

Variant links:

Genes affected

SEZ6L2 (HGNC:30844): (seizure related 6 homolog like 2) This gene encodes a seizure-related protein that is localized on the cell surface. The gene is located in a region of chromosome 16p11.2 that is thought to contain candidate genes for autism spectrum disorders (ASD), though there is no evidence directly implicating this gene in ASD. Increased expression of this gene has been found in lung cancers, and the protein is therefore considered to be a novel prognostic marker for lung cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

SEZ6L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23620003).

BP6

Variant 16-29897010-G-A is Benign according to our data. Variant chr16-29897010-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 221932.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2 link	c.323C>T	p.Thr108Ile	missense_variant	Exon 3 of 18	ENST00000617533.5	NP_001230261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L2	ENST00000617533.5 link	c.323C>T	p.Thr108Ile	missense_variant	Exon 3 of 18	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432124

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

41552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25616

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38764

South Asian (SAS)

AF:

0.00

AC:

AN:

83560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101650

Other (OTH)

AF:

0.00

AC:

AN:

59416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anophthalmia-microphthalmia syndrome

Benign:1

Jan 01, 2013

Paul Sabatier University EA-4555, Paul Sabatier University

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

.;T;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;.;.;.

PhyloP100

4.4

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.86

N;N;N;.;.

REVEL

Benign

0.073

Sift

Pathogenic

0.0

D;D;D;.;.

Sift4G

Benign

0.086

T;T;T;T;.

Polyphen

0.94

.;P;.;.;.

Vest4

0.51

MutPred

0.35

Loss of glycosylation at T108 (P = 0.0059);Loss of glycosylation at T108 (P = 0.0059);.;Loss of glycosylation at T108 (P = 0.0059);.;

MVP

0.57

MPC

1.2

ClinPred

0.54

GERP RS

5.4

Varity_R

0.16

gMVP

0.48

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over