3-42568931-C-T

Position:

• chr3-42568931-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032970.4(SEC22C):​c.116G>A​(p.Ser39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC22C NM_032970.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.860

Genes affected

SEC22C (HGNC:16828): (SEC22 homolog C, vesicle trafficking protein) This gene encodes a member of the SEC22 family of vesicle trafficking proteins. The encoded protein is localized to the endoplasmic reticulum and may play a role in the early stages of ER-Golgi protein trafficking. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

SEC22C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093428254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC22C	NM_032970.4	c.116G>A	p.Ser39Asn	missense_variant	2/7	ENST00000264454.8	NP_116752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC22C	ENST00000264454.8	c.116G>A	p.Ser39Asn	missense_variant	2/7	1	NM_032970.4	ENSP00000264454.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.116G>A (p.S39N) alteration is located in exon 2 (coding exon 1) of the SEC22C gene. This alteration results from a G to A substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by an asparagine (N). 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	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.1
DANN	Benign	0.95
DEOGEN2	Benign	0.034	.;.;.;T;.;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.29	T;.;T;T;T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.093	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L;L;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N
REVEL	Benign	0.012
Sift	Benign	0.16	T;T;T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;.;.;.;.
Polyphen		0.039	B;B;B;B;.;.;.;.
Vest4		0.084
MutPred		0.34		Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);Loss of phosphorylation at S39 (P = 0.1031);
MVP		0.28
MPC		0.17
ClinPred		0.15	T
GERP RS		2.5
Varity_R		0.035
gMVP		0.27

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: rs1384707342; hg19: chr3-42610423;