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GeneBe

5-134661373-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021982.3(SEC24A):c.352A>C(p.Thr118Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

SEC24A
NM_021982.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
Variant links:
Genes affected
SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07939309).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC24ANM_021982.3 linkuse as main transcriptc.352A>C p.Thr118Pro missense_variant 2/23 ENST00000398844.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24AENST00000398844.7 linkuse as main transcriptc.352A>C p.Thr118Pro missense_variant 2/232 NM_021982.3 P1O95486-1
SEC24AENST00000322887.8 linkuse as main transcriptc.352A>C p.Thr118Pro missense_variant 2/131 O95486-2

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152146
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000601
AC:
15
AN:
249574
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135402
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000800
AC:
117
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000770
AC XY:
56
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000962
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsAug 09, 2021The c.352A>C (p.T118P) alteration is located in exon 2 (coding exon 2) of the SEC24A gene. This alteration results from a A to C substitution at nucleotide position 352, causing the threonine (T) at amino acid position 118 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
0.058
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.16
Cadd
Benign
12
Dann
Benign
0.89
DEOGEN2
Benign
0.013
T;.
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.77
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.58
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-0.29
T
MutationAssessor
Benign
0.55
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.81
N;N
REVEL
Uncertain
0.32
Sift
Benign
0.069
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.0
B;.
Vest4
0.19
MutPred
0.12
Loss of phosphorylation at T118 (P = 0.0284);Loss of phosphorylation at T118 (P = 0.0284);
MVP
0.66
MPC
0.13
ClinPred
0.034
T
GERP RS
1.9
Varity_R
0.13
gMVP
0.16

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: rs745680774; hg19: chr5-133997063; API