rs12941884

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178860.5(SEZ6):c.2417T>C(p.Met806Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,832 control chromosomes in the GnomAD database, including 17,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2045 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15183 hom. )

Consequence

SEZ6
NM_178860.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.18

Publications

36 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040315986).

BP6

Variant 17-28957425-A-G is Benign according to our data. Variant chr17-28957425-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SEZ6	NM_178860.5 link	c.2417T>C	p.Met806Thr	missense_variant	Exon 12 of 17	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.2417T>C	p.Met806Thr	missense_variant	Exon 12 of 17	1	NM_178860.5	ENSP00000312942.11		Q53EL9-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23727

AN:

152048

Hom.:

2041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.149

GnomAD2 exomes

AF:

0.153

AC:

38239

AN:

249192

AF XY:

0.156

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.138

AC:

202001

AN:

1461666

Hom.:

15183

Cov.:

AF XY:

0.142

AC XY:

102995

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.212

AC:

7084

AN:

33480

American (AMR)

AF:

0.155

AC:

6927

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

3817

AN:

26134

East Asian (EAS)

AF:

0.0970

AC:

3849

AN:

39700

South Asian (SAS)

AF:

0.255

AC:

22014

AN:

86254

European-Finnish (FIN)

AF:

0.126

AC:

6739

AN:

53400

Middle Eastern (MID)

AF:

0.162

AC:

936

AN:

5768

European-Non Finnish (NFE)

AF:

0.128

AC:

141793

AN:

1111846

Other (OTH)

AF:

0.146

AC:

8842

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11243

22487

33730

44974

56217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5260

10520

15780

21040

26300

<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:

0.156

AC:

23753

AN:

152166

Hom.:

2045

Cov.:

AF XY:

0.157

AC XY:

11668

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.211

AC:

8748

AN:

41508

American (AMR)

AF:

0.155

AC:

2367

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

494

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

553

AN:

5180

South Asian (SAS)

AF:

0.253

AC:

1222

AN:

4822

European-Finnish (FIN)

AF:

0.122

AC:

1290

AN:

10608

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8625

AN:

67974

Other (OTH)

AF:

0.147

AC:

311

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1057

2114

3170

4227

5284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.138

Hom.:

5439

Bravo

AF:

0.159

TwinsUK

AF:

0.128

AC:

476

ALSPAC

AF:

0.124

AC:

476

ESP6500AA

AF:

0.198

AC:

773

ESP6500EA

AF:

0.124

AC:

1033

ExAC

AF:

0.155

AC:

18769

Asia WGS

AF:

0.195

AC:

682

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0030

.;T;T;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.087

T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.61

N;.;N;.;.

PhyloP100

2.2

PrimateAI

Uncertain

0.52

PROVEAN

Benign

1.3

N;.;.;.;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;.;.;.;T

Sift4G

Benign

0.74

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.019

MPC

0.31

ClinPred

0.0016

GERP RS

3.6

Varity_R

0.084

gMVP

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over