6-107921915-GAAAAAC-GGGGG

Variant names:

• chr6-107921916-AAAAAC-GGGG
• rs1554237221
• NM_007214.5:c.340-12_340-7delGTTTTTinsCCCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_007214.5(SEC63):​c.340-12_340-7delGTTTTTinsCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SEC63 NM_007214.5 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.208
• Publications: 0 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• polycystic liver disease 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 6-107921916-AAAAAC-GGGG is Benign according to our data. Variant chr6-107921916-AAAAAC-GGGG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 189837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC63	NM_007214.5	c.340-12_340-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 3 of 20	ENST00000369002.9	NP_009145.1
SEC63	XM_047418130.1	c.172-12_172-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 3 of 20		XP_047274086.1
SEC63	XM_047418131.1	c.-81-12_-81-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 2 of 19		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC63	ENST00000369002.9	c.340-12_340-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 3 of 20	1	NM_007214.5	ENSP00000357998.4
SEC63	ENST00000429168.1	c.172-12_172-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 3 of 7	5		ENSP00000403144.1
SEC63	ENST00000484803.5	n.262-12_262-7delGTTTTTinsCCCC		splice_region_variant, intron_variant	Intron 3 of 6	2

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 21, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic liver disease 2 Benign:1

Jul 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=60/40	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1554237221; hg19: chr6-108243120;