rs12917712

Variant names:

• chr16-29871169-C-T
• rs12917712
• NM_001243332.2:c.*530G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243332.2(SEZ6L2):​c.*530G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 166,222 control chromosomes in the GnomAD database, including 11,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10525 hom., cov: 30)
  • Exomes 𝑓: 0.27 (631 hom.)
• Consequence: SEZ6L2 NM_001243332.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 34 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2	c.*530G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000617533.5	NP_001230261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.*530G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54240 AN: 151424 Hom.: 10490 Cov.: 30

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.266 AC: 3907 AN: 14678 Hom.: 631 Cov.: 0 AF XY: 0.267 AC XY: 2077 AN XY: 7788

African (AFR) AF: 0.490 AC: 287 AN: 586

American (AMR) AF: 0.191 AC: 529 AN: 2770

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 51 AN: 222

East Asian (EAS) AF: 0.286 AC: 427 AN: 1492

South Asian (SAS) AF: 0.204 AC: 331 AN: 1622

European-Finnish (FIN) AF: 0.305 AC: 67 AN: 220

Middle Eastern (MID) AF: 0.111 AC: 2 AN: 18

European-Non Finnish (NFE) AF: 0.288 AC: 2073 AN: 7202

Other (OTH) AF: 0.256 AC: 140 AN: 546

GnomAD4 genome AF: 0.358 AC: 54318 AN: 151544 Hom.: 10525 Cov.: 30 AF XY: 0.355 AC XY: 26258 AN XY: 74054

African (AFR) AF: 0.516 AC: 21268 AN: 41240

American (AMR) AF: 0.232 AC: 3531 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 858 AN: 3458

East Asian (EAS) AF: 0.313 AC: 1608 AN: 5140

South Asian (SAS) AF: 0.187 AC: 898 AN: 4802

European-Finnish (FIN) AF: 0.339 AC: 3557 AN: 10490

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21724 AN: 67902

Other (OTH) AF: 0.285 AC: 600 AN: 2104

Alfa AF: 0.333 Hom.: 19310

Bravo AF: 0.359

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs12917712; hg19: chr16-29882490;