Genetic Variant NM_007214.5:c.*3574_*3575insGAC (chr6-107868129-T-TGTC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_007214.5(SEC63):c.*3574_*3575insGAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.96 ( 70533 hom., cov: 0)

Exomes 𝑓: 1.0 ( 2 hom. )

Consequence

SEC63
NM_007214.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.332

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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, 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 -10 ACMG points.

BP6

Variant 6-107868129-T-TGTC is Benign according to our data. Variant chr6-107868129-T-TGTC is described in ClinVar as Benign. ClinVar VariationId is 354813.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC63	NM_007214.5	MANE Select	c.3574_3575insGAC		3_prime_UTR	Exon 21 of 21	NP_009145.1	Q9UGP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC63	ENST00000369002.9	TSL:1 MANE Select	c.3574_3575insGAC		3_prime_UTR	Exon 21 of 21	ENSP00000357998.4	Q9UGP8

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146231

AN:

152028

Hom.:

70477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.969

Gnomad AMI

AF:

0.949

Gnomad AMR

AF:

0.964

Gnomad ASJ

AF:

0.977

Gnomad EAS

AF:

0.761

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

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:

0.962

AC:

146346

AN:

152146

Hom.:

70533

Cov.:

AF XY:

0.959

AC XY:

71324

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.969

AC:

40244

AN:

41516

American (AMR)

AF:

0.964

AC:

14740

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.977

AC:

3391

AN:

3470

East Asian (EAS)

AF:

0.761

AC:

3923

AN:

5158

South Asian (SAS)

AF:

0.960

AC:

4624

AN:

4816

European-Finnish (FIN)

AF:

0.940

AC:

9928

AN:

10562

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.975

AC:

66291

AN:

68020

Other (OTH)

AF:

0.970

AC:

2050

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

268

536

805

1073

1341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.973

Hom.:

7736

Bravo

AF:

0.962

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_007214.5:c.3574_3575insGAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over