rs869025256

chr16-29897010-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.40

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 221932.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L2	NM_001243332.2	c.323C>T	p.Thr108Ile	missense_variant	3/18	ENST00000617533.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.323C>T	p.Thr108Ile	missense_variant	3/18	1	NM_001243332.2	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

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: 1 AN: 1432124 Hom.: 0 Cov.: 36 AF XY: 0.00000141 AC XY: 1 AN XY: 710416

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N;.;.;.
MutationTaster	Benign	0.73	D;D;N;N
PrimateAI	Uncertain	0.77	T
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	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs869025256; hg19: chr16-29908331;