NM_007214.5:c.340-9T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007214.5(SEC63):c.340-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0028 ( 2 hom. )

Consequence

SEC63
NM_007214.5 intron

Scores

Splicing: ADA: 0.00002456

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.208

Publications

2 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: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 6-107921918-A-G is Benign according to our data. Variant chr6-107921918-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 403427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0081 (25/3088) while in subpopulation NFE AF = 0.00198 (2/1010). AF 95% confidence interval is 0.000351. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEC63	NM_007214.5 link	c.340-9T>C	intron_variant	Intron 3 of 20	ENST00000369002.9	NP_009145.1	Q9UGP8A0A0S2Z5M1
SEC63	XM_047418130.1 link	c.172-9T>C	intron_variant	Intron 3 of 20		XP_047274086.1
SEC63	XM_047418131.1 link	c.-81-9T>C	intron_variant	Intron 2 of 19		XP_047274087.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC63	ENST00000369002.9 link	c.340-9T>C	intron_variant	Intron 3 of 20	1	NM_007214.5	ENSP00000357998.4	Q9UGP8
SEC63	ENST00000429168.1 link	c.172-9T>C	intron_variant	Intron 3 of 7	5		ENSP00000403144.1	A6PVC9
SEC63	ENST00000484803.5 link	n.262-9T>C	intron_variant	Intron 3 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00781

AC:

AN:

3072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000867

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.0500

GnomAD2 exomes

AF:

0.000361

AC:

AN:

174382

AF XY:

0.000317

show subpopulations

Gnomad AFR exome

AF:

0.0000912

Gnomad AMR exome

AF:

0.0000443

Gnomad ASJ exome

AF:

0.00775

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000861

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.00282

AC:

194

AN:

68712

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

AN XY:

33880

show subpopulations

African (AFR)

AF:

0.000859

AC:

AN:

4656

American (AMR)

AF:

0.00

AC:

AN:

1318

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

150

AN:

1004

East Asian (EAS)

AF:

0.00

AC:

AN:

4708

South Asian (SAS)

AF:

0.00

AC:

AN:

1968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000380

AC:

AN:

50004

Other (OTH)

AF:

0.00765

AC:

AN:

2744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00810

AC:

AN:

3088

Hom.:

Cov.:

AF XY:

0.00927

AC XY:

AN XY:

1510

show subpopulations

African (AFR)

AF:

0.00172

AC:

AN:

1166

American (AMR)

AF:

0.00

AC:

AN:

206

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

276

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

232

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00198

AC:

AN:

1010

Other (OTH)

AF:

0.0476

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.578

Hom.:

1812

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: No change to splice consensus -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.49

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0040

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over