rs33991574

Variant names:

• chr17-28963951-T-TG
• rs11450637
• NM_178860.5:c.1240+10dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_178860.5(SEZ6):​c.1240+10dupC 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
• Publications: 6 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 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.1240+10dupC		intron	N/A	NP_849191.3	Q53EL9-1
	SEZ6	NM_001098635.2		c.1240+10dupC		intron	N/A	NP_001092105.1	Q53EL9-3
	SEZ6	NM_001290202.2		c.865+10dupC		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.1240+10_1240+11insC		intron	N/A	ENSP00000312942.11	Q53EL9-1
	SEZ6	ENST00000540632.6	TSL:1	c.1018+10_1018+11insC		intron	N/A	ENSP00000437650.2	H0YF95
	SEZ6	ENST00000360295.13	TSL:5	c.1240+10_1240+11insC		intron	N/A	ENSP00000353440.9	Q53EL9-3

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

GnomAD2 exomes AF: 0.514 AC: 119382 AN: 232150 AF XY: 0.512

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 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

African (AFR) AF: 0.920 AC: 30670 AN: 33330

American (AMR) AF: 0.452 AC: 19595 AN: 43366

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 13392 AN: 25900

East Asian (EAS) AF: 0.334 AC: 13185 AN: 39434

South Asian (SAS) AF: 0.532 AC: 44866 AN: 84294

European-Finnish (FIN) AF: 0.537 AC: 28314 AN: 52760

Middle Eastern (MID) AF: 0.569 AC: 3247 AN: 5704

European-Non Finnish (NFE) AF: 0.510 AC: 564250 AN: 1107268

Other (OTH) AF: 0.529 AC: 31717 AN: 59996

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

African (AFR) AF: 0.900 AC: 37367 AN: 41516

American (AMR) AF: 0.520 AC: 7948 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1662 AN: 5166

South Asian (SAS) AF: 0.526 AC: 2534 AN: 4820

European-Finnish (FIN) AF: 0.543 AC: 5743 AN: 10568

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34436 AN: 67968

Other (OTH) AF: 0.585 AC: 1235 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs11450637;

hg19: chr17-27290969;