10-73759735-C-T

Variant names:

• chr10-73759735-C-T
• rs145252752
• NM_198597.3:c.422C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198597.3(SEC24C):​c.422C>T​(p.Ser141Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC24C NM_198597.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20953721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24C	NM_198597.3	c.422C>T	p.Ser141Phe	missense_variant	Exon 4 of 23	ENST00000345254.9	NP_940999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24C	ENST00000345254.9	c.422C>T	p.Ser141Phe	missense_variant	Exon 4 of 23	1	NM_198597.3	ENSP00000321845.6
SEC24C	ENST00000465076.5	n.422C>T		non_coding_transcript_exon_variant	Exon 4 of 22	1		ENSP00000437000.1
SEC24C	ENST00000339365.2	c.422C>T	p.Ser141Phe	missense_variant	Exon 5 of 24	5		ENSP00000343405.2
SEC24C	ENST00000635550.1	n.286C>T		non_coding_transcript_exon_variant	Exon 3 of 23	2		ENSP00000489351.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	0.064
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.056	T;T
Polyphen		0.49	P;P
Vest4		0.30
MutPred		0.41		Loss of glycosylation at S141 (P = 0.0142);Loss of glycosylation at S141 (P = 0.0142);
MVP		0.48
MPC		0.015
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.094
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

Other links and lift over

dbSNP: rs145252752; hg19: chr10-75519493;