rs675117

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007214.5(SEC63):c.564C>T(p.Asn188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,605,432 control chromosomes in the GnomAD database, including 591,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57651 hom., cov: 33)

Exomes 𝑓: 0.86 ( 533972 hom. )

Consequence

SEC63
NM_007214.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.536

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 6-107912725-G-A is Benign according to our data. Variant chr6-107912725-G-A is described in ClinVar as [Benign]. Clinvar id is 95474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-107912725-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.536 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SEC63	NM_007214.5 linkuse as main transcript	c.564C>T	p.Asn188=	synonymous_variant	6/21	ENST00000369002.9	NP_009145.1
SEC63	XM_047418130.1 linkuse as main transcript	c.396C>T	p.Asn132=	synonymous_variant	6/21		XP_047274086.1
SEC63	XM_047418131.1 linkuse as main transcript	c.144C>T	p.Asn48=	synonymous_variant	5/20		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SEC63	ENST00000369002.9 linkuse as main transcript	c.564C>T	p.Asn188=	synonymous_variant	6/21	1	NM_007214.5	ENSP00000357998	P1
SEC63	ENST00000429168.1 linkuse as main transcript	c.396C>T	p.Asn132=	synonymous_variant	6/8	5		ENSP00000403144
SEC63	ENST00000484803.5 linkuse as main transcript	n.486C>T		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes

AF:

0.869

AC:

132207

AN:

152148

Hom.:

57605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.904

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.882

Gnomad ASJ

AF:

0.870

Gnomad EAS

AF:

0.710

Gnomad SAS

AF:

0.902

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.861

Gnomad OTH

AF:

0.867

GnomAD3 exomes

AF:

0.859

AC:

214598

AN:

249874

Hom.:

92420

AF XY:

0.859

AC XY:

116055

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.872

Gnomad EAS exome

AF:

0.720

Gnomad SAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.856

Gnomad OTH exome

AF:

0.858

GnomAD4 exome

AF:

0.856

AC:

1243944

AN:

1453166

Hom.:

533972

Cov.:

AF XY:

0.857

AC XY:

619680

AN XY:

723466

show subpopulations

Gnomad4 AFR exome

AF:

0.907

Gnomad4 AMR exome

AF:

0.901

Gnomad4 ASJ exome

AF:

0.866

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.897

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.858

Gnomad4 OTH exome

AF:

0.860

GnomAD4 genome

AF:

0.869

AC:

132311

AN:

152266

Hom.:

57651

Cov.:

AF XY:

0.867

AC XY:

64514

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.904

Gnomad4 AMR

AF:

0.883

Gnomad4 ASJ

AF:

0.870

Gnomad4 EAS

AF:

0.710

Gnomad4 SAS

AF:

0.902

Gnomad4 FIN

AF:

0.828

Gnomad4 NFE

AF:

0.861

Gnomad4 OTH

AF:

0.865

Alfa

AF:

0.863

Hom.:

82382

Bravo

AF:

0.873

Asia WGS

AF:

0.798

AC:

2775

AN:

3478

EpiCase

AF:

0.854

EpiControl

AF:

0.850

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 15, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Polycystic liver disease 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.1

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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