Genetic Variant SEC63:c.340-8T>G (chr6-107921917-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007214.5(SEC63):c.340-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 0)

Consequence

SEC63
NM_007214.5 splice_region, intron

Scores

Splicing: ADA: 0.00005054

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

3 publications found

Variant links:

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

SEC63 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SEC63	NM_007214.5 link	c.340-8T>G	splice_region_variant, intron_variant	Intron 3 of 20	ENST00000369002.9	NP_009145.1
SEC63	XM_047418130.1 link	c.172-8T>G	splice_region_variant, intron_variant	Intron 3 of 20		XP_047274086.1
SEC63	XM_047418131.1 link	c.-81-8T>G	splice_region_variant, intron_variant	Intron 2 of 19		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SEC63	ENST00000369002.9 link	c.340-8T>G	splice_region_variant, intron_variant	Intron 3 of 20	1	NM_007214.5	ENSP00000357998.4
SEC63	ENST00000429168.1 link	c.172-8T>G	splice_region_variant, intron_variant	Intron 3 of 7	5		ENSP00000403144.1
SEC63	ENST00000484803.5 link	n.262-8T>G	splice_region_variant, intron_variant	Intron 3 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

11670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000857

AC:

AN:

11670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1496

American (AMR)

AF:

0.00114

AC:

AN:

880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

146

East Asian (EAS)

AF:

0.00

AC:

AN:

260

South Asian (SAS)

AF:

0.00

AC:

AN:

114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

7480

Other (OTH)

AF:

0.00

AC:

AN:

128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.83

(source)

DANN

Benign

0.45

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.018

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over