10-73760396-T-G

Position:

• chr10-73760396-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198597.3(SEC24C):​c.850+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,575,090 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (25 hom.)
• Consequence: SEC24C NM_198597.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-73760396-T-G is Benign according to our data. Variant chr10-73760396-T-G is described in ClinVar as [Benign]. Clinvar id is 782290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 443 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24C	NM_198597.3	c.850+10T>G		intron_variant		ENST00000345254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24C	ENST00000345254.9	c.850+10T>G		intron_variant		1	NM_198597.3	P1

Frequencies

GnomAD3 genomes AF: 0.00291 AC: 443 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00487

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00270 AC: 601 AN: 222682 Hom.: 3 AF XY: 0.00260 AC XY: 316 AN XY: 121386

Gnomad AFR exome AF: 0.000994

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad SAS exome AF: 0.000183

Gnomad FIN exome AF: 0.000857

Gnomad NFE exome AF: 0.00442

Gnomad OTH exome AF: 0.00419

GnomAD4 exome AF: 0.00432 AC: 6143 AN: 1422762 Hom.: 25 Cov.: 32 AF XY: 0.00418 AC XY: 2943 AN XY: 704280

Gnomad4 AFR exome AF: 0.000549

Gnomad4 AMR exome AF: 0.00274

Gnomad4 ASJ exome AF: 0.0000410

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.00525

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.00291 AC: 443 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74498

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00487

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00291 Hom.: 2

Bravo AF: 0.00293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.16
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs118063873; hg19: chr10-75520154;