chr17-28963951-T-TG

Position:

• chr17-28963951-T-TG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_178860.5(SEZ6):​c.1240+10_1240+11insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,604,148 control chromosomes in the GnomAD database, including 228,868 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (31201 hom., cov: 0)
  • Exomes 𝑓: 0.52 (197667 hom.)
• Consequence: SEZ6 NM_178860.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

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]

LOC105371716 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6	NM_178860.5	c.1240+10_1240+11insC		intron_variant		ENST00000317338.17	NP_849191.3
LOC105371716	XR_001752822.2	n.1807+10546dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEZ6	ENST00000317338.17	c.1240+10_1240+11insC		intron_variant		1	NM_178860.5	ENSP00000312942	A2

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93263 AN: 151978 Hom.: 31150 Cov.: 0

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.591

GnomAD3 exomes AF: 0.514 AC: 119382 AN: 232150 Hom.: 32103 AF XY: 0.512 AC XY: 64485 AN XY: 125938

Gnomad AFR exome AF: 0.909

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.539

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.519

GnomAD4 exome AF: 0.516 AC: 749236 AN: 1452052 Hom.: 197667 Cov.: 41 AF XY: 0.515 AC XY: 371361 AN XY: 721280

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.614 AC: 93361 AN: 152096 Hom.: 31201 Cov.: 0 AF XY: 0.611 AC XY: 45425 AN XY: 74360

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.585

Alfa AF: 0.549 Hom.: 5350

Bravo AF: 0.623

Asia WGS AF: 0.452 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11450637; hg19: chr17-27290969;