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

Variant names:

• chr6-107921918-A-G
• rs1569555
• NM_007214.5:c.340-9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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

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

ACMG classification

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 VariationId 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.

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.340-9T>C		intron	N/A	NP_009145.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC63	ENST00000369002.9	TSL:1 MANE Select	c.340-9T>C		intron	N/A	ENSP00000357998.4
	SEC63	ENST00000884697.1		c.427-9T>C		intron	N/A	ENSP00000554756.1
	SEC63	ENST00000884696.1		c.421-9T>C		intron	N/A	ENSP00000554755.1

Frequencies

GnomAD3 genomes AF: 0.00781 AC: 24 AN: 3072 Hom.: 0 Cov.: 0

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: 63 AN: 174382 AF XY: 0.000317

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.: 2 Cov.: 0 AF XY: 0.00280 AC XY: 95 AN XY: 33880

African (AFR) AF: 0.000859 AC: 4 AN: 4656

American (AMR) AF: 0.00 AC: 0 AN: 1318

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 150 AN: 1004

East Asian (EAS) AF: 0.00 AC: 0 AN: 4708

South Asian (SAS) AF: 0.00 AC: 0 AN: 1968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.000380 AC: 19 AN: 50004

Other (OTH) AF: 0.00765 AC: 21 AN: 2744

GnomAD4 genome AF: 0.00810 AC: 25 AN: 3088 Hom.: 0 Cov.: 0 AF XY: 0.00927 AC XY: 14 AN XY: 1510

African (AFR) AF: 0.00172 AC: 2 AN: 1166

American (AMR) AF: 0.00 AC: 0 AN: 206

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 19 AN: 86

East Asian (EAS) AF: 0.00 AC: 0 AN: 276

South Asian (SAS) AF: 0.00 AC: 0 AN: 46

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 232

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00198 AC: 2 AN: 1010

Other (OTH) AF: 0.0476 AC: 2 AN: 42

Alfa AF: 0.578 Hom.: 1812

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
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)

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

Other links and lift over

dbSNP: rs1569555; hg19: chr6-108243122;