Variant 10-73759630-G-A 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.317G>A(p.Gly106Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,523,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

SEC24C
NM_198597.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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=0.22883761).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24C	NM_198597.3 linkuse as main transcript	c.317G>A	p.Gly106Glu	missense_variant	4/23	ENST00000345254.9	NP_940999.1	P53992-1A0A024QZM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEC24C	ENST00000345254.9 linkuse as main transcript	c.317G>A	p.Gly106Glu	missense_variant	4/23	1	NM_198597.3	ENSP00000321845.6	P53992-1
SEC24C	ENST00000465076.5 linkuse as main transcript	n.317G>A		non_coding_transcript_exon_variant	4/22	1		ENSP00000437000.1	G5EA31
SEC24C	ENST00000339365.2 linkuse as main transcript	c.317G>A	p.Gly106Glu	missense_variant	5/24	5		ENSP00000343405.2	P53992-1
SEC24C	ENST00000635550.1 linkuse as main transcript	n.181G>A		non_coding_transcript_exon_variant	3/23	2		ENSP00000489351.1	A0A0U1RR58

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000535

AC:

AN:

187002

Hom.:

AF XY:

0.00000990

AC XY:

AN XY:

100990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000948

AC:

AN:

1371588

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

674508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000112

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

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

Sep 28, 2022

The c.317G>A (p.G106E) 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 317, causing the glycine (G) at amino acid position 106 to be replaced by a glutamic acid (E). 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

0.22

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.086

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.38

Sift

Benign

0.16

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.20

B;B

Vest4

0.50

MVP

0.84

MPC

0.021

ClinPred

0.11

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.20

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