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GeneBe

10-73766103-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198597.3(SEC24C):c.1500C>A(p.Ser500Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000862 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

3
15

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.574
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.017150402).
BS2
High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC24CNM_198597.3 linkuse as main transcriptc.1500C>A p.Ser500Arg missense_variant 11/23 ENST00000345254.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24CENST00000345254.9 linkuse as main transcriptc.1500C>A p.Ser500Arg missense_variant 11/231 NM_198597.3 P1P53992-1
SEC24CENST00000465076.5 linkuse as main transcriptc.1500C>A p.Ser500Arg missense_variant, NMD_transcript_variant 11/221
SEC24CENST00000339365.2 linkuse as main transcriptc.1500C>A p.Ser500Arg missense_variant 12/245 P1P53992-1
SEC24CENST00000635550.1 linkuse as main transcriptc.*890C>A 3_prime_UTR_variant, NMD_transcript_variant 11/232

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000192
AC:
48
AN:
250594
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135518
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000497
Gnomad EAS exome
AF:
0.00223
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000883
AC:
129
AN:
1460902
Hom.:
0
Cov.:
32
AF XY:
0.0000867
AC XY:
63
AN XY:
726808
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00295
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152268
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00174
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000805
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.000165
AC:
20
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Microcephaly Uncertain:1
Uncertain significance, no assertion criteria providedresearchDepartment of Pediatrics, Samsung Medical Center, Samsung Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.39
Cadd
Benign
21
Dann
Benign
0.95
DEOGEN2
Benign
0.057
T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.42
N;N
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.78
N;N
REVEL
Benign
0.11
Sift
Benign
0.29
T;T
Sift4G
Benign
0.22
T;T
Polyphen
0.0060
B;B
Vest4
0.21
MutPred
0.46
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.44
MPC
0.49
ClinPred
0.034
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.13

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: rs200016285; hg19: chr10-75525861; API