10-73759752-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_198597.3(SEC24C):c.439G>A(p.Gly147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,606,298 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).
Frequency
Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00090 ( 1 hom. )
Consequence
SEC24C
NM_198597.3 missense
NM_198597.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 1.37
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033474088).
BS2
?
High AC in GnomAd4 at 84 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC24C | NM_198597.3 | c.439G>A | p.Gly147Ser | missense_variant | 4/23 | ENST00000345254.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC24C | ENST00000345254.9 | c.439G>A | p.Gly147Ser | missense_variant | 4/23 | 1 | NM_198597.3 | P1 | |
SEC24C | ENST00000465076.5 | c.439G>A | p.Gly147Ser | missense_variant, NMD_transcript_variant | 4/22 | 1 | |||
SEC24C | ENST00000339365.2 | c.439G>A | p.Gly147Ser | missense_variant | 5/24 | 5 | P1 | ||
SEC24C | ENST00000635550.1 | c.303G>A | p.Ala101= | synonymous_variant, NMD_transcript_variant | 3/23 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000552 AC: 84AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000395 AC: 96AN: 242952Hom.: 0 AF XY: 0.000342 AC XY: 45AN XY: 131642
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GnomAD4 exome AF: 0.000895 AC: 1302AN: 1454088Hom.: 1 Cov.: 32 AF XY: 0.000828 AC XY: 599AN XY: 723494
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GnomAD4 genome ? AF: 0.000552 AC: 84AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000471 AC XY: 35AN XY: 74364
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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 submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.439G>A (p.G147S) alteration is located in exon 5 (coding exon 3) of the SEC24C gene. This alteration results from a G to A substitution at nucleotide position 439, causing the glycine (G) at amino acid position 147 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.012
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at