rs146798574

Variant names:

• chr10-73760307-C-G
• rs146798574
• NM_198597.3:c.771C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-73760307-C-G
• chr10-73760307-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_198597.3(SEC24C):​c.771C>G​(p.Gly257Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00889 in 1,613,340 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (85 hom.)
• Consequence: SEC24C NM_198597.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0800
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288823 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-73760307-C-G is Benign according to our data. Variant chr10-73760307-C-G is described in ClinVar as Benign. ClinVar VariationId is 771741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.08 with no splicing effect.
• BS2: High AC in GnomAd4 at 1103 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198597.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24C	NM_198597.3	MANE Select	c.771C>G	p.Gly257Gly	synonymous	Exon 5 of 23	NP_940999.1	P53992-1
	SEC24C	NM_004922.4		c.771C>G	p.Gly257Gly	synonymous	Exon 6 of 24	NP_004913.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24C	ENST00000345254.9	TSL:1 MANE Select	c.771C>G	p.Gly257Gly	synonymous	Exon 5 of 23	ENSP00000321845.6	P53992-1
	SEC24C	ENST00000465076.5	TSL:1	n.771C>G		non_coding_transcript_exon	Exon 5 of 22	ENSP00000437000.1	G5EA31
	SEC24C	ENST00000893972.1		c.771C>G	p.Gly257Gly	synonymous	Exon 5 of 23	ENSP00000564031.1

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1103 AN: 152168 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00758 AC: 1900 AN: 250530 AF XY: 0.00823

Gnomad AFR exome AF: 0.00259

Gnomad AMR exome AF: 0.00471

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00505

Gnomad NFE exome AF: 0.00970

Gnomad OTH exome AF: 0.00866

GnomAD4 exome AF: 0.00906 AC: 13236 AN: 1461054 Hom.: 85 Cov.: 32 AF XY: 0.00933 AC XY: 6779 AN XY: 726882

African (AFR) AF: 0.00251 AC: 84 AN: 33480

American (AMR) AF: 0.00561 AC: 251 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 423 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00926 AC: 799 AN: 86254

European-Finnish (FIN) AF: 0.00524 AC: 276 AN: 52640

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.00973 AC: 10815 AN: 1111970

Other (OTH) AF: 0.00866 AC: 523 AN: 60388

GnomAD4 genome AF: 0.00724 AC: 1103 AN: 152286 Hom.: 9 Cov.: 32 AF XY: 0.00713 AC XY: 531 AN XY: 74460

African (AFR) AF: 0.00282 AC: 117 AN: 41556

American (AMR) AF: 0.00516 AC: 79 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4826

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 715 AN: 68010

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00738 Hom.: 1

Bravo AF: 0.00683

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0123

EpiControl AF: 0.0114

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.60
PhyloP100		-0.080
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146798574; hg19: chr10-75520065;