chr3-42568881-A-G

Position:

• chr3-42568881-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032970.4(SEC22C):​c.166T>C​(p.Cys56Arg) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC22C NM_032970.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.238

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023273498).
• BP6: Variant 3-42568881-A-G is Benign according to our data. Variant chr3-42568881-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3317087.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC22C	NM_032970.4	c.166T>C	p.Cys56Arg	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.166T>C	p.Cys56Arg	missense_variant	2/7	1	NM_032970.4	ENSP00000264454.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.5
DANN	Benign	0.31
DEOGEN2	Benign	0.013	.;.;.;T;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.27	T;.;T;T;T;T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.023	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.85	N;N;N;N;.;.;.;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.3	N;N;N;N;N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.50	T;T;T;T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;.;.;.;.
Polyphen		0.0	B;B;B;B;.;.;.;.
Vest4		0.097
MutPred		0.43		Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);
MVP		0.32
MPC		0.29
ClinPred		0.024	T
GERP RS		-2.1
Varity_R		0.065
gMVP		0.33

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: rs1703429828; hg19: chr3-42610373;