6-107912725-G-T

Position:

• chr6-107912725-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007214.5(SEC63):​c.564C>A​(p.Asn188Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N188N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEC63 NM_007214.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC63	NM_007214.5	c.564C>A	p.Asn188Lys	missense_variant	6/21	ENST00000369002.9
SEC63	XM_047418130.1	c.396C>A	p.Asn132Lys	missense_variant	6/21
SEC63	XM_047418131.1	c.144C>A	p.Asn48Lys	missense_variant	5/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC63	ENST00000369002.9	c.564C>A	p.Asn188Lys	missense_variant	6/21	1	NM_007214.5	P1
SEC63	ENST00000429168.1	c.396C>A	p.Asn132Lys	missense_variant	6/8	5
SEC63	ENST00000484803.5	n.486C>A		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1455200 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	0.000067	P
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.98	D;.
Vest4		0.90
MutPred		0.54		Gain of ubiquitination at N188 (P = 0.0238);.;
MVP		0.68
MPC		1.0
ClinPred		1.0	D
GERP RS		-2.9
Varity_R		0.71
gMVP		0.97

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

Other links and lift over

dbSNP: rs675117; hg19: chr6-108233929;