rs200003656

Variant names:

• chr22-26292811-C-T
• rs200003656
• ENST00000402979.1:c.-182C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-26292811-C-T
• chr22-26292811-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000402979.1(SEZ6L):​c.-182C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,944 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SEZ6L ENST00000402979.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499
• Publications: 2 publications found

Genes affected

SEZ6L (HGNC:10763): (seizure related 6 homolog like) Predicted to act upstream of or within adult locomotory behavior; nervous system development; and regulation of protein kinase C signaling. Predicted to be located in endoplasmic reticulum and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

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=0.042051286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402979.1. 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
	SEZ6L	NM_021115.5	MANE Select	c.500C>T	p.Pro167Leu	missense	Exon 2 of 17	NP_066938.2
	SEZ6L	NM_001184773.2		c.500C>T	p.Pro167Leu	missense	Exon 2 of 17	NP_001171702.1	Q9BYH1-6
	SEZ6L	NM_001184774.2		c.500C>T	p.Pro167Leu	missense	Exon 2 of 16	NP_001171703.1	Q9BYH1-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	ENST00000402979.1	TSL:1	c.-182C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000384733.1	B0QYH5
	SEZ6L	ENST00000403121.5	TSL:1	c.-182C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000384838.1	B0QYH4
	SEZ6L	ENST00000248933.11	TSL:1 MANE Select	c.500C>T	p.Pro167Leu	missense	Exon 2 of 17	ENSP00000248933.6	Q9BYH1-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 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

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 249950 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461592 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111846

Other (OTH) AF: 0.0000331 AC: 2 AN: 60376

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.068
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.50
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.044
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.020	D
Polyphen		0.69	P
Vest4		0.13
MVP		0.10
MPC		0.10
ClinPred		0.031	T
GERP RS		-3.2
Varity_R		0.031
gMVP		0.14
Mutation Taster		=90/10	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: rs200003656; hg19: chr22-26688777; COSMIC: COSV50661171;