6-107868129-T-TGTC

Position:

• chr6-107868129-T-TGTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007214.5(SEC63):​c.*3574_*3575insGAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70533 hom., cov: 0)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: SEC63 NM_007214.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.332

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 -10 ACMG points.

• BP6: Variant 6-107868129-T-TGTC is Benign according to our data. Variant chr6-107868129-T-TGTC is described in ClinVar as [Benign]. Clinvar id is 354813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC63	NM_007214.5	c.*3574_*3575insGAC		3_prime_UTR_variant	21/21	ENST00000369002.9
SEC63	XM_047418130.1	c.*3574_*3575insGAC		3_prime_UTR_variant	21/21
SEC63	XM_047418131.1	c.*3574_*3575insGAC		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC63	ENST00000369002.9	c.*3574_*3575insGAC		3_prime_UTR_variant	21/21	1	NM_007214.5	P1

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146231 AN: 152028 Hom.: 70477 Cov.: 0

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.949

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.971

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.962 AC: 146346 AN: 152146 Hom.: 70533 Cov.: 0 AF XY: 0.959 AC XY: 71324 AN XY: 74354

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.960

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.975

Gnomad4 OTH AF: 0.970

Alfa AF: 0.973 Hom.: 7736

Bravo AF: 0.962

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polycystic liver disease 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10685655; hg19: chr6-108189333;