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GeneBe

10-73760299-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198597.3(SEC24C):c.763C>G(p.Pro255Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,613,514 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

1
2
14

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0058408678).
BP6
Variant 10-73760299-C-G is Benign according to our data. Variant chr10-73760299-C-G is described in ClinVar as [Benign]. Clinvar id is 718500.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 645 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC24CNM_198597.3 linkuse as main transcriptc.763C>G p.Pro255Ala missense_variant 5/23 ENST00000345254.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24CENST00000345254.9 linkuse as main transcriptc.763C>G p.Pro255Ala missense_variant 5/231 NM_198597.3 P1P53992-1

Frequencies

GnomAD3 genomes
AF:
0.00424
AC:
645
AN:
152186
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
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:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00104
AC:
261
AN:
250678
Hom.:
1
AF XY:
0.000797
AC XY:
108
AN XY:
135562
show subpopulations
Gnomad AFR exome
AF:
0.0150
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000415
AC:
606
AN:
1461210
Hom.:
2
Cov.:
32
AF XY:
0.000373
AC XY:
271
AN XY:
726966
show subpopulations
Gnomad4 AFR exome
AF:
0.0161
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
AF:
0.00423
AC:
644
AN:
152304
Hom.:
3
Cov.:
32
AF XY:
0.00400
AC XY:
298
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0146
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000156
Hom.:
0
Bravo
AF:
0.00513
ESP6500AA
AF:
0.0138
AC:
61
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00121
AC:
147
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.53
Cadd
Benign
19
Dann
Benign
0.96
DEOGEN2
Benign
0.20
T;T;T
Eigen
Benign
-0.086
Eigen_PC
Benign
0.012
FATHMM_MKL
Uncertain
0.85
D
MetaRNN
Benign
0.0058
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;.
MutationTaster
Benign
0.99
D;D;D;D;D;N
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-4.5
D;D;.
REVEL
Benign
0.065
Sift
Benign
0.12
T;T;.
Sift4G
Uncertain
0.026
D;D;D
Polyphen
0.0040
B;B;.
Vest4
0.32
MVP
0.37
MPC
0.013
ClinPred
0.036
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.23
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs150235476; hg19: chr10-75520057; API