rs755290172

Variant names:

• chr16-29877408-C-G
• rs755290172
• NM_001243332.2:c.1772G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-29877408-C-G
• chr16-29877408-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001243332.2(SEZ6L2):​c.1772G>C​(p.Arg591Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SEZ6L2 NM_001243332.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2	c.1772G>C	p.Arg591Pro	missense_variant	Exon 11 of 18	ENST00000617533.5	NP_001230261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.1772G>C	p.Arg591Pro	missense_variant	Exon 11 of 18	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000203 AC: 5 AN: 245984 Hom.: 0 AF XY: 0.0000224 AC XY: 3 AN XY: 133870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460194 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;.;T;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	.;.;L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.6	D;N;N;N;.
REVEL	Benign	0.26
Sift	Benign	0.20	T;T;T;T;.
Sift4G	Uncertain	0.039	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.77
MutPred		0.63		.;.;Loss of MoRF binding (P = 0.0293);.;Loss of MoRF binding (P = 0.0293);
MVP		0.49
MPC		1.4
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.62
gMVP		0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs755290172; hg19: chr16-29888729;