Genetic Variant NM_178860.5:c.1240+10dupC (chr17-28963951-T-TG) – ACMG Classification: Benign (-8 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.265

Publications

6 publications found

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:

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:

LOC105371716 (HGNC:):

LOC105371716 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6	NM_178860.5 link	c.1240+10dupC		intron_variant	Intron 5 of 16	ENST00000317338.17	NP_849191.3	Q53EL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6	ENST00000317338.17 link	c.1240+10_1240+11insC		intron_variant	Intron 5 of 16	1	NM_178860.5	ENSP00000312942.11		Q53EL9-1

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93263

AN:

151978

Hom.:

31150

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.515

AC XY:

371361

AN XY:

721280

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19007

38014

57020

76027

95034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16416

32832

49248

65664

82080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.614

AC:

93361

AN:

152096

Hom.:

31201

Cov.:

AF XY:

0.611

AC XY:

45425

AN XY:

74360

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1610

3219

4829

6438

8048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over