Variant 6-107868124-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007214.5(SEC63):c.*3580G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,152 control chromosomes in the GnomAD database, including 70,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.96 ( 70544 hom., cov: 30)

Exomes 𝑓: 1.0 ( 2 hom. )

Consequence

SEC63
NM_007214.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0110

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-107868124-C-T is Benign according to our data. Variant chr6-107868124-C-T is described in ClinVar as [Benign]. Clinvar id is 354812.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	Effect	#exon/exons	MANE
SEC63	NM_007214.5 linkuse as main transcript	c.*3580G>A	3_prime_UTR_variant	21/21	ENST00000369002.9
SEC63	XM_047418130.1 linkuse as main transcript	c.*3580G>A	3_prime_UTR_variant	21/21
SEC63	XM_047418131.1 linkuse as main transcript	c.*3580G>A	3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC63	ENST00000369002.9 linkuse as main transcript	c.*3580G>A		3_prime_UTR_variant	21/21	1	NM_007214.5	P1

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146249

AN:

152030

Hom.:

70488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.969

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.964

Gnomad ASJ

AF:

0.977

Gnomad EAS

AF:

0.762

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:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.962

AC:

146364

AN:

152148

Hom.:

70544

Cov.:

AF XY:

0.959

AC XY:

71329

AN XY:

74350

show subpopulations

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:

0.971

Hom.:

80778

Bravo

AF:

0.963

Asia WGS

AF:

0.874

AC:

3039

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Polycystic liver disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.83

CADD

Benign

3.9

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over