16-29897010-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243332.2(SEZ6L2):​c.323C>A​(p.Thr108Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T108I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SEZ6L2 NM_001243332.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22014362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2	c.323C>A	p.Thr108Asn	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	c.323C>A	p.Thr108Asn	missense_variant	Exon 3 of 18	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes Cov.: 32

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: 0.00 AC: 0 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: 9.08e-7 AC: 1 AN: 1101650

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	.;T;.;.;.
Eigen	Benign	0.066
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N;.;.;.
PhyloP100		4.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.26	N;N;N;.;.
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D;T;D;.;.
Sift4G	Benign	0.32	T;T;T;T;.
Polyphen		0.68	.;P;.;.;.
Vest4		0.47
MutPred		0.19		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		0.58
MPC		1.2
ClinPred		0.60	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.41

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: rs869025256; hg19: chr16-29908331;