rs1569557

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007214.5(SEC63):c.340-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,146,240 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00085 ( 1 hom., cov: 26)

Exomes 𝑓: 0.00049 ( 9 hom. )

Consequence

SEC63
NM_007214.5 splice_region, intron

Scores

Splicing: ADA: 0.00002116

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.208

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-107921916-A-G is Benign according to our data. Variant chr6-107921916-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 403425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000845 (104/123016) while in subpopulation AFR AF = 0.00149 (44/29588). AF 95% confidence interval is 0.00114. There are 1 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

BS2

High AC in GnomAd4 at 104 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEC63	NM_007214.5 link	c.340-7T>C	splice_region_variant, intron_variant	Intron 3 of 20	ENST00000369002.9	NP_009145.1	Q9UGP8A0A0S2Z5M1
SEC63	XM_047418130.1 link	c.172-7T>C	splice_region_variant, intron_variant	Intron 3 of 20		XP_047274086.1
SEC63	XM_047418131.1 link	c.-81-7T>C	splice_region_variant, intron_variant	Intron 2 of 19		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC63	ENST00000369002.9 link	c.340-7T>C	splice_region_variant, intron_variant	Intron 3 of 20	1	NM_007214.5	ENSP00000357998.4	Q9UGP8
SEC63	ENST00000429168.1 link	c.172-7T>C	splice_region_variant, intron_variant	Intron 3 of 7	5		ENSP00000403144.1	A6PVC9
SEC63	ENST00000484803.5 link	n.262-7T>C	splice_region_variant, intron_variant	Intron 3 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.000805

AC:

AN:

122998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000593

Gnomad ASJ

AF:

0.00629

Gnomad EAS

AF:

0.000466

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00699

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.00284

GnomAD2 exomes

AF:

0.000509

AC:

106

AN:

208188

AF XY:

0.000476

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.000359

Gnomad ASJ exome

AF:

0.00623

Gnomad EAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.000403

GnomAD4 exome

AF:

0.000491

AC:

502

AN:

1023224

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

265

AN XY:

518542

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

23624

American (AMR)

AF:

0.000717

AC:

AN:

34860

Ashkenazi Jewish (ASJ)

AF:

0.00734

AC:

153

AN:

20854

East Asian (EAS)

AF:

0.0000306

AC:

AN:

32644

South Asian (SAS)

AF:

0.0000909

AC:

AN:

65994

European-Finnish (FIN)

AF:

0.0000482

AC:

AN:

41510

Middle Eastern (MID)

AF:

0.000890

AC:

AN:

4492

European-Non Finnish (NFE)

AF:

0.000246

AC:

186

AN:

755596

Other (OTH)

AF:

0.00172

AC:

AN:

43650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000845

AC:

104

AN:

123016

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

59924

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

29588

American (AMR)

AF:

0.000592

AC:

AN:

13522

Ashkenazi Jewish (ASJ)

AF:

0.00629

AC:

AN:

3178

East Asian (EAS)

AF:

0.000467

AC:

AN:

4280

South Asian (SAS)

AF:

0.00

AC:

AN:

4054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7896

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.000399

AC:

AN:

57700

Other (OTH)

AF:

0.00282

AC:

AN:

1774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: No change to splice consensus -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic liver disease 2

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 14, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.4

(source)

DANN

Benign

0.63

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0060

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over