6-107868207-T-C

Position:

• chr6-107868207-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007214.5(SEC63):​c.*3497A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 128,186 control chromosomes in the GnomAD database, including 1,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1113 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SEC63 NM_007214.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-107868207-T-C is Benign according to our data. Variant chr6-107868207-T-C is described in ClinVar as [Benign]. Clinvar id is 354819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC63	NM_007214.5	c.*3497A>G		3_prime_UTR_variant	21/21	ENST00000369002.9
SEC63	XM_047418130.1	c.*3497A>G		3_prime_UTR_variant	21/21
SEC63	XM_047418131.1	c.*3497A>G		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC63	ENST00000369002.9	c.*3497A>G		3_prime_UTR_variant	21/21	1	NM_007214.5	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 17263 AN: 128072 Hom.: 1115 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0788

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0602

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.126

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.135 AC: 17262 AN: 128186 Hom.: 1113 Cov.: 31 AF XY: 0.142 AC XY: 8691 AN XY: 61400

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0788

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.123

Alfa AF: 0.102 Hom.: 1341

Bravo AF: 0.106

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polycystic liver disease 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.90
DANN	Benign	0.68

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: rs6933329; hg19: chr6-108189411;