10-73759752-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 1 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.37

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]

SEC24C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033474088).

BP6

Variant 10-73759752-G-A is Benign according to our data. Variant chr10-73759752-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2380866.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24C	NM_198597.3 link	c.439G>A	p.Gly147Ser	missense_variant	Exon 4 of 23	ENST00000345254.9	NP_940999.1	P53992-1A0A024QZM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC24C	ENST00000345254.9 link	c.439G>A	p.Gly147Ser	missense_variant	Exon 4 of 23	1	NM_198597.3	ENSP00000321845.6	P53992-1
SEC24C	ENST00000465076.5 link	n.439G>A		non_coding_transcript_exon_variant	Exon 4 of 22	1		ENSP00000437000.1	G5EA31
SEC24C	ENST00000339365.2 link	c.439G>A	p.Gly147Ser	missense_variant	Exon 5 of 24	5		ENSP00000343405.2	P53992-1
SEC24C	ENST00000635550.1 link	n.303G>A		non_coding_transcript_exon_variant	Exon 3 of 23	2		ENSP00000489351.1	A0A0U1RR58

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00110

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000395

AC:

AN:

242952

AF XY:

0.000342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000615

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000802

Gnomad OTH exome

AF:

0.000848

GnomAD4 exome

AF:

0.000895

AC:

1302

AN:

1454088

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

599

AN XY:

723494

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

AC:

AN:

33208

Gnomad4 AMR exome

AF:

0.0000468

AC:

AN:

42718

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25844

Gnomad4 EAS exome

AF:

0.0000507

AC:

AN:

39446

Gnomad4 SAS exome

AF:

0.0000352

AC:

AN:

85294

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51998

Gnomad4 NFE exome

AF:

0.00109

AC:

1208

AN:

1109794

Gnomad4 Remaining exome

AF:

0.00115

AC:

AN:

60048

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000552

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000121

AC:

0.000120592

AN:

0.000120592

Gnomad4 AMR

AF:

0.000262

AC:

0.000261712

AN:

0.000261712

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00110

AC:

0.00110233

AN:

0.00110233

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000740

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SEC24C: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

0.0087

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.74

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.52

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.027

B;B

Vest4

0.15

MVP

0.83

MPC

0.012

ClinPred

0.041

GERP RS

4.9

Varity_R

0.064

gMVP

0.11

Mutation Taster

=98/2

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over