rs675117

Positions:

• chr6-107912725-G-A
• chr6-107912725-G-C
• chr6-107912725-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.536

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]

ACMG classification

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	UniProt
SEC63	NM_007214.5	c.564C>T	p.Asn188=	synonymous_variant	6/21	ENST00000369002.9
SEC63	XM_047418130.1	c.396C>T	p.Asn132=	synonymous_variant	6/21
SEC63	XM_047418131.1	c.144C>T	p.Asn48=	synonymous_variant	5/20

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132207 AN: 152148 Hom.: 57605 Cov.: 33

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

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.: 32 AF XY: 0.857 AC XY: 619680 AN XY: 723466

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.: 33 AF XY: 0.867 AC XY: 64514 AN XY: 74438

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

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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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	Invitae	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

Other links and lift over

dbSNP: rs675117; hg19: chr6-108233929; COSMIC: COSV64598818; COSMIC: COSV64598818;