rs752018806

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_007214.5(SEC63):c.1703_1705delAAG(p.Glu568del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0025 in 1,612,242 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 16 hom. )

Consequence

SEC63
NM_007214.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:6

Conservation

PhyloP100: 6.33

Publications

4 publications found

Variant links:

Genes affected

SEC63 (HGNC:21082): (SEC63 homolog, protein translocation regulator) The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC62 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]

SEC63 Gene-Disease associations (from GenCC):

polycystic liver disease 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
polycystic liver disease 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEC63 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 6-107883115-ACTT-A is Benign according to our data. Variant chr6-107883115-ACTT-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 354899.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00261 (397/152262) while in subpopulation NFE AF = 0.00219 (149/68022). AF 95% confidence interval is 0.0019. There are 5 homozygotes in GnomAd4. There are 238 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SEC63	NM_007214.5 link	c.1703_1705delAAG	p.Glu568del	disruptive_inframe_deletion	Exon 17 of 21	ENST00000369002.9	NP_009145.1
SEC63	XM_047418130.1 link	c.1535_1537delAAG	p.Glu512del	disruptive_inframe_deletion	Exon 17 of 21		XP_047274086.1
SEC63	XM_047418131.1 link	c.1283_1285delAAG	p.Glu428del	disruptive_inframe_deletion	Exon 16 of 20		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SEC63	ENST00000369002.9 link	c.1703_1705delAAG	p.Glu568del	disruptive_inframe_deletion	Exon 17 of 21	1	NM_007214.5	ENSP00000357998.4
SEC63	ENST00000473746.1 link	n.350_352delAAG		non_coding_transcript_exon_variant	Exon 1 of 4	2
SEC63	ENST00000465210.1 link	n.-6_-4delAAG		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

397

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00369

AC:

926

AN:

250706

AF XY:

0.00356

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0169

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00249

AC:

3640

AN:

1459980

Hom.:

AF XY:

0.00244

AC XY:

1770

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33446

American (AMR)

AF:

0.000739

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

544

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0153

AC:

806

AN:

52728

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00187

AC:

2082

AN:

1111076

Other (OTH)

AF:

0.00277

AC:

167

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

176

353

529

706

882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.00261

AC:

397

AN:

152262

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41566

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0163

AC:

173

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00219

AC:

149

AN:

68022

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00454

Hom.:

Bravo

AF:

0.00153

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Aug 23, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Polycystic liver disease 1

Uncertain:1Benign:1

May 28, 2019

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic liver disease 2

Pathogenic:1

Jun 01, 2004

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

SEC63-related disorder

Benign:1

May 22, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.3

Mutation Taster

=38/62

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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