10-73760299-C-G

Variant names:

• chr10-73760299-C-G
• rs150235476
• NM_198597.3:c.763C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_198597.3(SEC24C):​c.763C>G​(p.Pro255Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,613,514 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (2 hom.)
• Consequence: SEC24C NM_198597.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.71

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058408678).
• BP6: Variant 10-73760299-C-G is Benign according to our data. Variant chr10-73760299-C-G is described in ClinVar as [Benign]. Clinvar id is 718500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24C	NM_198597.3	c.763C>G	p.Pro255Ala	missense_variant	Exon 5 of 23	ENST00000345254.9	NP_940999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24C	ENST00000345254.9	c.763C>G	p.Pro255Ala	missense_variant	Exon 5 of 23	1	NM_198597.3	ENSP00000321845.6

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152186 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00104 AC: 261 AN: 250678 AF XY: 0.000797

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000415 AC: 606 AN: 1461210 Hom.: 2 Cov.: 32 AF XY: 0.000373 AC XY: 271 AN XY: 726966

Gnomad4 AFR exome AF: 0.0161 AC: 539 AN: 33480

Gnomad4 AMR exome AF: 0.000425 AC: 19 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39698

Gnomad4 SAS exome AF: 0.0000348 AC: 3 AN: 86254

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52780

Gnomad4 NFE exome AF: 0.00000180 AC: 2 AN: 1111986

Gnomad4 Remaining exome AF: 0.000679 AC: 41 AN: 60386

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152304 Hom.: 3 Cov.: 32 AF XY: 0.00400 AC XY: 298 AN XY: 74484

Gnomad4 AFR AF: 0.0146 AC: 0.0145566 AN: 0.0145566

Gnomad4 AMR AF: 0.00229 AC: 0.00228728 AN: 0.00228728

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000147042 AN: 0.0000147042

Gnomad4 OTH AF: 0.00142 AC: 0.00141911 AN: 0.00141911

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.00513

ESP6500AA AF: 0.0138 AC: 61

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00121 AC: 147

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T;T;T
Eigen	Benign	-0.086
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.73	.;T;T
MetaRNN	Benign	0.0058	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.5	D;D;.
REVEL	Benign	0.065
Sift	Benign	0.12	T;T;.
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.0040	B;B;.
Vest4		0.32
MVP		0.37
MPC		0.013
ClinPred		0.036	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.23
gMVP		0.29
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs150235476; hg19: chr10-75520057;