rs886041029

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 354899.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=2}. Variant chr6-107883115-ACTT-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC63	NM_007214.5 link	c.1703_1705delAAG	p.Glu568del	disruptive_inframe_deletion	Exon 17 of 21	ENST00000369002.9	NP_009145.1	Q9UGP8A0A0S2Z5M1
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	UniProt
SEC63	ENST00000369002.9 link	c.1703_1705delAAG	p.Glu568del	disruptive_inframe_deletion	Exon 17 of 21	1	NM_007214.5	ENSP00000357998.4	Q9UGP8
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

GnomAD3 exomes

AF:

0.00369

AC:

926

AN:

250706

Hom.:

AF XY:

0.00356

AC XY:

483

AN XY:

135556

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00277

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152262

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00189

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

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 23, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic liver disease 1

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Uncertain significance

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over