10-73751219-C-G

Variant summary

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

The NM_198597.3(SEC24C):​c.284C>G​(p.Pro95Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEC24C
NM_198597.3 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34
Variant links:
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]

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ACMG classification

Classification made for transcript

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
SEC24CNM_198597.3 linkuse as main transcriptc.284C>G p.Pro95Arg missense_variant 3/23 ENST00000345254.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24CENST00000345254.9 linkuse as main transcriptc.284C>G p.Pro95Arg missense_variant 3/231 NM_198597.3 P1P53992-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2022The c.284C>G (p.P95R) alteration is located in exon 4 (coding exon 2) of the SEC24C gene. This alteration results from a C to G substitution at nucleotide position 284, causing the proline (P) at amino acid position 95 to be replaced by an arginine (R). 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
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.79
.;T
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.2
M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.011
B;B
Vest4
0.71
MutPred
0.35
Gain of MoRF binding (P = 0.0041);Gain of MoRF binding (P = 0.0041);
MVP
0.76
MPC
0.071
ClinPred
0.99
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.67
gMVP
0.14

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: chr10-75510977; API