Variant 10-73760803-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198597.3(SEC24C):c.941A>C(p.Gln314Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 1 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09950948).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24C	NM_198597.3 linkuse as main transcript	c.941A>C	p.Gln314Pro	missense_variant	6/23	ENST00000345254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24C	ENST00000345254.9 linkuse as main transcript	c.941A>C	p.Gln314Pro	missense_variant	6/23	1	NM_198597.3	P1	P53992-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251358

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000151

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

Feb 15, 2023

The c.941A>C (p.Q314P) alteration is located in exon 7 (coding exon 5) of the SEC24C gene. This alteration results from a A to C substitution at nucleotide position 941, causing the glutamine (Q) at amino acid position 314 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

0.055

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.0041

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;N;.

MutationTaster

Benign

0.96

D;D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Benign

0.053

Sift

Benign

0.054

T;T;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.44

MutPred

0.38

Gain of glycosylation at Q314 (P = 0.0013);Gain of glycosylation at Q314 (P = 0.0013);.;

MVP

0.38

MPC

0.53

ClinPred

0.21

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.32

gMVP

0.67

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.

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