rs592939

Variant names:

• chr6-107868311-G-A
• rs592939
• NM_007214.5:c.*3393C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-107868311-G-A
• chr6-107868311-G-C
• chr6-107868311-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007214.5(SEC63):​c.*3393C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 152,062 control chromosomes in the GnomAD database, including 69,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69709 hom., cov: 30)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: SEC63 NM_007214.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.681
• 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• polycystic liver disease 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-107868311-G-A is Benign according to our data. Variant chr6-107868311-G-A is described in ClinVar as Benign. ClinVar VariationId is 354826.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.*3393C>T		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.*3393C>T		3_prime_UTR	Exon 21 of 21	ENSP00000357998.4	Q9UGP8

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145335 AN: 151938 Hom.: 69661 Cov.: 30

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.968

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.956 AC: 145441 AN: 152056 Hom.: 69709 Cov.: 30 AF XY: 0.954 AC XY: 70896 AN XY: 74314

African (AFR) AF: 0.951 AC: 39406 AN: 41450

American (AMR) AF: 0.962 AC: 14703 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3393 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3916 AN: 5158

South Asian (SAS) AF: 0.960 AC: 4624 AN: 4816

European-Finnish (FIN) AF: 0.940 AC: 9920 AN: 10552

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.975 AC: 66278 AN: 68002

Other (OTH) AF: 0.967 AC: 2046 AN: 2116

Alfa AF: 0.970 Hom.: 9254

Bravo AF: 0.957

Asia WGS AF: 0.871 AC: 3031 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Polycystic liver disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs592939; hg19: chr6-108189515;