20-18510899-A-G

Position:

• chr20-18510899-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006363.6(SEC23B):​c.64A>G​(p.Asn22Asp) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEC23B NM_006363.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23B	NM_006363.6	c.64A>G	p.Asn22Asp	missense_variant	2/20	ENST00000650089.1	NP_006354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1	c.64A>G	p.Asn22Asp	missense_variant	2/20		NM_006363.6	ENSP00000497473	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SEC23B: PM2, PM3, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.;T;T;.;.;.;T;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;.;D;D;.;D;D;D;.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Pathogenic	3.8	H;H;.;.;H;.;.;.;H;H
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.4	D;D;.;D;D;.;.;.;.;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D;.;D;D;.;.;.;.;D
Sift4G	Uncertain	0.0020	D;D;.;D;D;.;.;.;.;D
Polyphen		0.99	D;D;.;.;D;.;.;.;D;D
Vest4		0.96
MutPred		0.73		Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);
MVP		0.95
MPC		0.73
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18491543;