rs863223347

Variant names:

• chr17-28981408-GGTGGTGGTA-G
• rs863223347
• NM_178860.5:c.678_686delTACCACCAC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP3

The NM_178860.5(SEZ6):​c.678_686delTACCACCAC​(p.Thr227_Thr229del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEZ6 NM_178860.5 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.25
• Publications: 0 publications found

Genes affected

SEZ6 (HGNC:15955): (seizure related 6 homolog) The protein encoded by this gene is thought to contain five cysteine-rich motifs that are similar to sushi domains, as well as two domains similar to the amino terminal half of the CUB (for complement C1r/C1s, Uegf, Bmp1) domain. Mutations in this gene have been associated with febrile seizures. [provided by RefSeq, Jul 2016]

PIPOX (HGNC:17804): (pipecolic acid and sarcosine oxidase) Enables L-pipecolate oxidase activity and sarcosine oxidase activity. Involved in L-lysine catabolic process to acetyl-CoA via L-pipecolate. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371716 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-28981408-GGTGGTGGTA-G is Pathogenic according to our data. Variant chr17-28981408-GGTGGTGGTA-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 208383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP3: Nonframeshift variant in repetitive region in NM_178860.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178860.5. 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
	SEZ6	NM_178860.5	MANE Select	c.678_686delTACCACCAC	p.Thr227_Thr229del	disruptive_inframe_deletion	Exon 2 of 17	NP_849191.3	Q53EL9-1
	SEZ6	NM_001098635.2		c.678_686delTACCACCAC	p.Thr227_Thr229del	disruptive_inframe_deletion	Exon 2 of 17	NP_001092105.1	Q53EL9-3
	SEZ6	NM_001290202.2		c.303_311delTACCACCAC	p.Thr102_Thr104del	disruptive_inframe_deletion	Exon 2 of 17	NP_001277131.1	Q53EL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6	ENST00000317338.17	TSL:1 MANE Select	c.678_686delTACCACCAC	p.Thr227_Thr229del	disruptive_inframe_deletion	Exon 2 of 17	ENSP00000312942.11	Q53EL9-1
	SEZ6	ENST00000540632.6	TSL:1	c.456_464delTACCACCAC	p.Thr153_Thr155del	disruptive_inframe_deletion	Exon 1 of 16	ENSP00000437650.2	H0YF95
	SEZ6	ENST00000360295.13	TSL:5	c.678_686delTACCACCAC	p.Thr227_Thr229del	disruptive_inframe_deletion	Exon 2 of 17	ENSP00000353440.9	Q53EL9-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Childhood-onset schizophrenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2
Mutation Taster		=139/61	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs863223347;

hg19: chr17-27308426;