16-29897010-G-A

Variant names:

• chr16-29897010-G-A
• rs869025256
• NM_001243332.2:c.323C>T

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243332.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L2	NM_001243332.2	MANE Select	c.323C>T	p.Thr108Ile	missense	Exon 3 of 18	NP_001230261.1
	SEZ6L2	NM_201575.4		c.323C>T	p.Thr108Ile	missense	Exon 3 of 17	NP_963869.2
	SEZ6L2	NM_001243333.2		c.191C>T	p.Thr64Ile	missense	Exon 2 of 17	NP_001230262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L2	ENST00000617533.5	TSL:1 MANE Select	c.323C>T	p.Thr108Ile	missense	Exon 3 of 18	ENSP00000481917.1
	SEZ6L2	ENST00000308713.9	TSL:1	c.323C>T	p.Thr108Ile	missense	Exon 3 of 17	ENSP00000312550.5
	SEZ6L2	ENST00000346932.9	TSL:1	c.323C>T	p.Thr108Ile	missense	Exon 3 of 16	ENSP00000319215.6

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

African (AFR) AF: 0.00 AC: 0 AN: 33152

American (AMR) AF: 0.00 AC: 0 AN: 41552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38764

South Asian (SAS) AF: 0.00 AC: 0 AN: 83560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101650

Other (OTH) AF: 0.00 AC: 0 AN: 59416

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

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 v4.9

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
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.086	T
Polyphen		0.94	P
Vest4		0.51
MutPred		0.35		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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs869025256; hg19: chr16-29908331;