rs6112008

Positions:

• chr20-18524553-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006363.6(SEC23B):​c.487C>A​(p.Leu163Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: SEC23B NM_006363.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23B	NM_006363.6	c.487C>A	p.Leu163Met	missense_variant	5/20	ENST00000650089.1	NP_006354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1	c.487C>A	p.Leu163Met	missense_variant	5/20		NM_006363.6	ENSP00000497473	P1

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	Benign	0.089
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T;T;T;T;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	.;.;D;.;D;.;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.8	M;M;.;M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N;N;N;N;.;.;N
REVEL	Uncertain	0.61
Sift	Benign	0.061	T;T;T;T;.;.;T
Sift4G	Uncertain	0.051	T;T;T;T;.;.;T
Polyphen		0.39	B;B;.;B;.;B;B
Vest4		0.67
MutPred		0.69		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.65
MPC		0.36
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.58
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6112008; hg19: chr20-18505197;