rs768976080

Variant names:

• chr10-73746870-T-C
• rs768976080
• NM_198597.3:c.38T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-73746870-T-C
• chr10-73746870-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_198597.3(SEC24C):​c.38T>C​(p.Phe13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,460,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: SEC24C NM_198597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16987097).
• BS2: High AC in GnomAdExome4 at 76 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.38T>C	p.Phe13Ser	missense	Exon 2 of 23	NP_940999.1	P53992-1
	SEC24C	NM_004922.4		c.38T>C	p.Phe13Ser	missense	Exon 3 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.38T>C	p.Phe13Ser	missense	Exon 2 of 23	ENSP00000321845.6	P53992-1
	SEC24C	ENST00000465076.5	TSL:1	n.38T>C		non_coding_transcript_exon	Exon 2 of 22	ENSP00000437000.1	G5EA31
	SEC24C	ENST00000893972.1		c.38T>C	p.Phe13Ser	missense	Exon 2 of 23	ENSP00000564031.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249824 AF XY: 0.00000741

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000520 AC: 76 AN: 1460178 Hom.: 0 Cov.: 30 AF XY: 0.0000509 AC XY: 37 AN XY: 726268

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1111316

Other (OTH) AF: 0.0000331 AC: 2 AN: 60332

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.17	T
Polyphen		0.079	B
Vest4		0.34
MutPred		0.32		Gain of glycosylation at F13 (P = 4e-04)
MVP		0.53
MPC		0.012
ClinPred		0.38	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.34
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs768976080; hg19: chr10-75506628;