Menu
GeneBe

10-73760803-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198597.3(SEC24C):c.941A>C(p.Gln314Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 1 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09950948).
BS2
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC24CNM_198597.3 linkuse as main transcriptc.941A>C p.Gln314Pro missense_variant 6/23 ENST00000345254.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24CENST00000345254.9 linkuse as main transcriptc.941A>C p.Gln314Pro missense_variant 6/231 NM_198597.3 P1P53992-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251358
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461828
Hom.:
1
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000852
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.000151

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 GeneticsFeb 15, 2023The c.941A>C (p.Q314P) alteration is located in exon 7 (coding exon 5) of the SEC24C gene. This alteration results from a A to C substitution at nucleotide position 941, causing the glutamine (Q) at amino acid position 314 to be replaced by a proline (P). 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
0.055
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.47
Cadd
Benign
21
Dann
Uncertain
0.98
DEOGEN2
Benign
0.20
T;T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.81
D
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.14
N;N;.
MutationTaster
Benign
0.96
D;D;D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.3
D;D;.
REVEL
Benign
0.053
Sift
Benign
0.054
T;T;.
Sift4G
Benign
0.14
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.44
MutPred
0.38
Gain of glycosylation at Q314 (P = 0.0013);Gain of glycosylation at Q314 (P = 0.0013);.;
MVP
0.38
MPC
0.53
ClinPred
0.21
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.32
gMVP
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1459039491; hg19: chr10-75520561; API