17-28957548-AG-A

Variant names:

• chr17-28957548-AG-A
• rs67322066
• NM_178860.5:c.2303-10delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178860.5(SEZ6):​c.2303-10delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,609,682 control chromosomes in the GnomAD database, including 16,126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1551 hom., cov: 30)
  • Exomes 𝑓: 0.14 (14575 hom.)
• Consequence: SEZ6 NM_178860.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.975
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-28957548-AG-A is Benign according to our data. Variant chr17-28957548-AG-A is described in ClinVar as Benign. ClinVar VariationId is 1294563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

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.2303-10delC		intron	N/A	NP_849191.3	Q53EL9-1
	SEZ6	NM_001098635.2		c.2303-10delC		intron	N/A	NP_001092105.1	Q53EL9-3
	SEZ6	NM_001290202.2		c.1928-10delC		intron	N/A	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.2303-10delC		intron	N/A	ENSP00000312942.11	Q53EL9-1
	SEZ6	ENST00000540632.6	TSL:1	c.2081-10delC		intron	N/A	ENSP00000437650.2	H0YF95
	SEZ6	ENST00000360295.13	TSL:5	c.2303-10delC		intron	N/A	ENSP00000353440.9	Q53EL9-3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21023 AN: 151996 Hom.: 1546 Cov.: 30

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.147 AC: 34916 AN: 237728 AF XY: 0.150

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.136 AC: 198173 AN: 1457568 Hom.: 14575 Cov.: 31 AF XY: 0.140 AC XY: 101117 AN XY: 724754

African (AFR) AF: 0.153 AC: 5097 AN: 33404

American (AMR) AF: 0.148 AC: 6510 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3774 AN: 25986

East Asian (EAS) AF: 0.0966 AC: 3828 AN: 39636

South Asian (SAS) AF: 0.254 AC: 21848 AN: 85922

European-Finnish (FIN) AF: 0.126 AC: 6681 AN: 53180

Middle Eastern (MID) AF: 0.162 AC: 929 AN: 5752

European-Non Finnish (NFE) AF: 0.127 AC: 140975 AN: 1109592

Other (OTH) AF: 0.142 AC: 8531 AN: 60220

GnomAD4 genome AF: 0.138 AC: 21044 AN: 152114 Hom.: 1551 Cov.: 30 AF XY: 0.140 AC XY: 10432 AN XY: 74372

African (AFR) AF: 0.149 AC: 6181 AN: 41502

American (AMR) AF: 0.148 AC: 2259 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5168

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1294 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8615 AN: 67966

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.137 Hom.: 263

Bravo AF: 0.139

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs67322066; hg19: chr17-27284566; COSMIC: COSV57977343; COSMIC: COSV57977343;