10-73760147-G-A

Variant summary

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

The ENST00000345254.9(SEC24C):​c.611G>A​(p.Arg204Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SEC24C
ENST00000345254.9 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69
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=0.0812144).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEC24CNM_198597.3 linkuse as main transcriptc.611G>A p.Arg204Gln missense_variant 5/23 ENST00000345254.9 NP_940999.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEC24CENST00000345254.9 linkuse as main transcriptc.611G>A p.Arg204Gln missense_variant 5/231 NM_198597.3 ENSP00000321845 P1P53992-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251120
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

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 GeneticsDec 17, 2023The c.611G>A (p.R204Q) alteration is located in exon 6 (coding exon 4) of the SEC24C gene. This alteration results from a G to A substitution at nucleotide position 611, causing the arginine (R) at amino acid position 204 to be replaced by a glutamine (Q). 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
0.081
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
16
DANN
Benign
0.88
DEOGEN2
Benign
0.016
T;T;T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
.;T;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.081
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.3
L;L;.
MutationTaster
Benign
1.0
D;D;N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.40
N;N;.
REVEL
Benign
0.19
Sift
Benign
0.71
T;T;.
Sift4G
Benign
0.38
T;T;T
Polyphen
0.85
P;P;.
Vest4
0.18
MutPred
0.30
Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);.;
MVP
0.79
MPC
0.012
ClinPred
0.092
T
GERP RS
3.8
Varity_R
0.024
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs752246592; hg19: chr10-75519905; API