4-109433919-C-T

Variant names:

• chr4-109433919-C-T
• NM_006323.5:c.50C>T

Variant summary

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

The NM_006323.5(SEC24B):​c.50C>T​(p.Pro17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,166,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: SEC24B NM_006323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.418

Genes affected

SEC24B (HGNC:10704): (SEC24 homolog B, 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 is thought to be a cargo-binding component of the COPII vesicle, and is thought to be involved in the transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in this gene have been associated with neural tube defects, and are thought to be a result of a disruption in interactions with the protein encoded by the VANGL planar cell polarity protein 2 (VANGL2) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24B-AS1 (HGNC:44003): (SEC24B antisense RNA 1) This lncRNA contains a single Alu element which, along with 1/2-sbsRNA3, appears to target the 3' UTR Alu element in MTAP. Downregulation of the RNA appears to up-regulate the target. [provided by RefSeq, Feb 2011]

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=0.21596071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24B	NM_006323.5	c.50C>T	p.Pro17Leu	missense_variant	Exon 1 of 24	ENST00000265175.5	NP_006314.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24B	ENST00000265175.5	c.50C>T	p.Pro17Leu	missense_variant	Exon 1 of 24	1	NM_006323.5	ENSP00000265175.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000257 AC: 3 AN: 1166494 Hom.: 0 Cov.: 30 AF XY: 0.00000352 AC XY: 2 AN XY: 568510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000207

Gnomad4 OTH exome AF: 0.0000216

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50C>T (p.P17L) alteration is located in exon 1 (coding exon 1) of the SEC24B gene. This alteration results from a C to T substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.88	N;N;N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.016, 0.0090	.;B;B
Vest4		0.28
MutPred		0.33		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.62
MPC		0.15
ClinPred		0.54	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.16

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: chr4-110355075;