chr10-73759743-C-G

Position:

• chr10-73759743-C-G

Variant summary

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

The NM_198597.3(SEC24C):​c.430C>G​(p.Gln144Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SEC24C NM_198597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

Genes affected

SEC24C (HGNC:10705): (SEC24 homolog C, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The product of this gene may play a role in shaping the vesicle, as well as in cargo selection and concentration. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

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=0.3116714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24C	NM_198597.3	c.430C>G	p.Gln144Glu	missense_variant	4/23	ENST00000345254.9	NP_940999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC24C	ENST00000345254.9	c.430C>G	p.Gln144Glu	missense_variant	4/23	1	NM_198597.3	ENSP00000321845.6
SEC24C	ENST00000465076.5	n.430C>G		non_coding_transcript_exon_variant	4/22	1		ENSP00000437000.1
SEC24C	ENST00000339365.2	c.430C>G	p.Gln144Glu	missense_variant	5/24	5		ENSP00000343405.2
SEC24C	ENST00000635550.1	n.294C>G		non_coding_transcript_exon_variant	3/23	2		ENSP00000489351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Sep 14, 2023

The c.430C>G (p.Q144E) alteration is located in exon 5 (coding exon 3) of the SEC24C gene. This alteration results from a C to G substitution at nucleotide position 430, causing the glutamine (Q) at amino acid position 144 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.069	T;T
Polyphen		0.68	P;P
Vest4		0.43
MutPred		0.30		Gain of phosphorylation at S146 (P = 0.1343);Gain of phosphorylation at S146 (P = 0.1343);
MVP		0.77
MPC		0.013
ClinPred		0.43	T
GERP RS		5.8
Varity_R		0.21
gMVP		0.19

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: chr10-75519501;