3-169982802-A-G

Variant names:

• chr3-169982802-A-G
• NM_003262.4:c.347A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003262.4(SEC62):​c.347A>G​(p.Glu116Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SEC62 NM_003262.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98

Genes affected

SEC62 (HGNC:11846): (SEC62 homolog, preprotein translocation factor) 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 SEC63 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]

SEC62-AS1 (HGNC:40586): (SEC62 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26444417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC62	NM_003262.4	c.347A>G	p.Glu116Gly	missense_variant	Exon 4 of 8	ENST00000337002.9	NP_003253.1
SEC62	XM_011513114.4	c.233A>G	p.Glu78Gly	missense_variant	Exon 5 of 9		XP_011511416.1
SEC62	XM_047448819.1	c.233A>G	p.Glu78Gly	missense_variant	Exon 5 of 9		XP_047304775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC62	ENST00000337002.9	c.347A>G	p.Glu116Gly	missense_variant	Exon 4 of 8	1	NM_003262.4	ENSP00000337688.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448400 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 720388

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: 0.00000362

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347A>G (p.E116G) alteration is located in exon 4 (coding exon 4) of the SEC62 gene. This alteration results from a A to G substitution at nucleotide position 347, causing the glutamic acid (E) at amino acid position 116 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.27
Sift	Benign	0.22	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.32	B;B
Vest4		0.34
MutPred		0.30		Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);
MVP		0.33
MPC		1.2
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.10
gMVP		0.077

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169700590;