rs118204000

Positions:

• chr14-39067256-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_006364.4(SEC23A):​c.1144T>C​(p.Phe382Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC23A NM_006364.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.20

Genes affected

SEC23A (HGNC:10701): (SEC23 homolog A, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family. It is part of a protein complex and found in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles. This protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The encoded protein is suggested to play a role in the ER-Golgi protein trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951
• PP5: Variant 14-39067256-A-G is Pathogenic according to our data. Variant chr14-39067256-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1228.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23A	NM_006364.4	c.1144T>C	p.Phe382Leu	missense_variant	10/20	ENST00000307712.11
SEC23A	XM_005267262.2	c.1144T>C	p.Phe382Leu	missense_variant	10/21
SEC23A	XM_011536355.4	c.1144T>C	p.Phe382Leu	missense_variant	10/21
SEC23A	XM_017020928.3	c.1144T>C	p.Phe382Leu	missense_variant	10/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23A	ENST00000307712.11	c.1144T>C	p.Phe382Leu	missense_variant	10/20	1	NM_006364.4	P1
SEC23A	ENST00000545328.6	c.1057T>C	p.Phe353Leu	missense_variant	9/19	2
SEC23A	ENST00000537403.5	c.538T>C	p.Phe180Leu	missense_variant	6/16	2
SEC23A	ENST00000553925.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Craniolenticulosutural dysplasia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.5	.;M;.
MutationTaster	Benign	1.0	A;A;A;A;A
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.70, 0.78	.;P;P
Vest4		0.91
MutPred		0.85		.;Loss of methylation at K383 (P = 0.0311);.;
MVP		0.93
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.85

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: rs118204000; hg19: chr14-39536460;