NM_007214.5:c.564C>T

Variant names:

• chr6-107912725-G-A
• rs675117
• NM_007214.5:c.564C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007214.5(SEC63):​c.564C>T​(p.Asn188Asn) 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
• Publications: 23 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• polycystic liver disease 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 95474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC63	NM_007214.5	MANE Select	c.564C>T	p.Asn188Asn	synonymous	Exon 6 of 21	NP_009145.1	Q9UGP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC63	ENST00000369002.9	TSL:1 MANE Select	c.564C>T	p.Asn188Asn	synonymous	Exon 6 of 21	ENSP00000357998.4	Q9UGP8
	SEC63	ENST00000884697.1		c.651C>T	p.Asn217Asn	synonymous	Exon 7 of 22	ENSP00000554756.1
	SEC63	ENST00000884696.1		c.645C>T	p.Asn215Asn	synonymous	Exon 7 of 22	ENSP00000554755.1

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

GnomAD2 exomes AF: 0.859 AC: 214598 AN: 249874 AF XY: 0.859

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 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

African (AFR) AF: 0.907 AC: 30216 AN: 33322

American (AMR) AF: 0.901 AC: 40226 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 22565 AN: 26054

East Asian (EAS) AF: 0.642 AC: 25427 AN: 39614

South Asian (SAS) AF: 0.897 AC: 77150 AN: 86030

European-Finnish (FIN) AF: 0.833 AC: 44427 AN: 53334

Middle Eastern (MID) AF: 0.865 AC: 4949 AN: 5720

European-Non Finnish (NFE) AF: 0.858 AC: 947344 AN: 1104352

Other (OTH) AF: 0.860 AC: 51640 AN: 60072

GnomAD4 genome AF: 0.869 AC: 132311 AN: 152266 Hom.: 57651 Cov.: 33 AF XY: 0.867 AC XY: 64514 AN XY: 74438

African (AFR) AF: 0.904 AC: 37584 AN: 41558

American (AMR) AF: 0.883 AC: 13490 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3677 AN: 5180

South Asian (SAS) AF: 0.902 AC: 4353 AN: 4828

European-Finnish (FIN) AF: 0.828 AC: 8776 AN: 10594

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58553 AN: 68028

Other (OTH) AF: 0.865 AC: 1830 AN: 2116

Alfa AF: 0.864 Hom.: 95299

Bravo AF: 0.873

Asia WGS AF: 0.798 AC: 2775 AN: 3478

EpiCase AF: 0.854

EpiControl AF: 0.850

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	2	Polycystic liver disease 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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