16-29873682-C-T

Variant names:

• chr16-29873682-C-T
• rs763216398
• NM_001243332.2:c.2152G>A

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.2152G>A​(p.Ala718Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000609 in 1,610,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: SEZ6L2 NM_001243332.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562
• 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=0.09156826).
• BP6: Variant 16-29873682-C-T is Benign according to our data. Variant chr16-29873682-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3440333.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L2	NM_001243332.2	MANE Select	c.2152G>A	p.Ala718Thr	missense	Exon 13 of 18	NP_001230261.1	A0A087WYL5
	SEZ6L2	NM_201575.4		c.2152G>A	p.Ala718Thr	missense	Exon 13 of 17	NP_963869.2	Q6UXD5-1
	SEZ6L2	NM_001243333.2		c.2020G>A	p.Ala674Thr	missense	Exon 12 of 17	NP_001230262.1	Q6UXD5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L2	ENST00000617533.5	TSL:1 MANE Select	c.2152G>A	p.Ala718Thr	missense	Exon 13 of 18	ENSP00000481917.1	A0A087WYL5
	SEZ6L2	ENST00000308713.9	TSL:1	c.2152G>A	p.Ala718Thr	missense	Exon 13 of 17	ENSP00000312550.5	Q6UXD5-1
	SEZ6L2	ENST00000350527.7	TSL:1	c.1942G>A	p.Ala648Thr	missense	Exon 13 of 18	ENSP00000310206.3	Q6UXD5-3

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000650 AC: 16 AN: 246134 AF XY: 0.0000975

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.0000497

Gnomad NFE exome AF: 0.0000809

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000583 AC: 85 AN: 1458218 Hom.: 0 Cov.: 32 AF XY: 0.0000620 AC XY: 45 AN XY: 725294

African (AFR) AF: 0.0000897 AC: 3 AN: 33452

American (AMR) AF: 0.0000224 AC: 1 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86042

European-Finnish (FIN) AF: 0.0000581 AC: 3 AN: 51592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1110848

Other (OTH) AF: 0.0000829 AC: 5 AN: 60292

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74360

African (AFR) AF: 0.0000483 AC: 2 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.060	N
PhyloP100		0.56
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.10
Sift	Benign	0.32	T
Sift4G	Benign	0.11	T
Polyphen		0.85	P
Vest4		0.12
MutPred		0.46		Gain of glycosylation at A718 (P = 0.0141)
MVP		0.36
MPC		0.34
ClinPred		0.020	T
GERP RS		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.48
Mutation Taster		=81/19	polymorphism

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: rs763216398; hg19: chr16-29885003;