rs1554237221

Positions:

• chr6-107921915-GAAAAAC-GGGG
• chr6-107921915-GAAAAAC-GGGGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The ENST00000369002.9(SEC63):​c.340-12_340-7delinsCCC variant causes a splice region, splice polypyrimidine tract, 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 ENST00000369002.9 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.208

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 -8 ACMG points.

• BP6: Variant 6-107921916-AAAAAC-GGG is Benign according to our data. Variant chr6-107921916-AAAAAC-GGG is described in ClinVar as [Likely_benign]. Clinvar id is 95472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC63	NM_007214.5	c.340-12_340-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000369002.9	NP_009145.1
SEC63	XM_047418130.1	c.172-12_172-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047274086.1
SEC63	XM_047418131.1	c.-81-12_-81-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC63	ENST00000369002.9	c.340-12_340-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007214.5	ENSP00000357998	P1
SEC63	ENST00000429168.1	c.172-12_172-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000403144
SEC63	ENST00000484803.5	n.262-12_262-7delinsCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 14, 2014	- -

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: rs1554237221; hg19: chr6-108243120;