Variant 17-28957548-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_178860.5(SEZ6):c.2303-10del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.975

Variant links:

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]

SEZ6 links:

LOC105371716 (HGNC:):

LOC105371716 links:

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]

PIPOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6	NM_178860.5 linkuse as main transcript	c.2303-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000317338.17
LOC105371716	XR_001752822.2 linkuse as main transcript	n.1807+4145del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6	ENST00000317338.17 linkuse as main transcript	c.2303-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_178860.5	A2	Q53EL9-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21023

AN:

151996

Hom.:

1546

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.147

AC:

34916

AN:

237728

Hom.:

2800

AF XY:

0.150

AC XY:

19458

AN XY:

129336

show subpopulations

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 SAS exome

AF:

0.262

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.:

AF XY:

0.140

AC XY:

101117

AN XY:

724754

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.0966

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.138

AC:

21044

AN:

152114

Hom.:

1551

Cov.:

AF XY:

0.140

AC XY:

10432

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.137

Hom.:

263

Bravo

AF:

0.139

Asia WGS

AF:

0.191

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over