rs1391945564

Variant names:

• chr4-109463267-C-A
• rs1391945564
• NM_006323.5:c.500C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-109463267-C-A
• chr4-109463267-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006323.5(SEC24B):​c.500C>A​(p.Ala167Asp) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A167V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC24B NM_006323.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09553307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006323.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24B	NM_006323.5	MANE Select	c.500C>A	p.Ala167Asp	missense	Exon 2 of 24	NP_006314.2	O95487-1
	SEC24B	NM_001300813.3		c.593C>A	p.Ala198Asp	missense	Exon 3 of 25	NP_001287742.1	O95487-3
	SEC24B	NM_001318085.2		c.500C>A	p.Ala167Asp	missense	Exon 2 of 24	NP_001305014.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24B	ENST00000265175.5	TSL:1 MANE Select	c.500C>A	p.Ala167Asp	missense	Exon 2 of 24	ENSP00000265175.4	O95487-1
	SEC24B	ENST00000504968.6	TSL:1	c.593C>A	p.Ala198Asp	missense	Exon 3 of 25	ENSP00000428564.1	O95487-3
	SEC24B	ENST00000399100.6	TSL:1	c.500C>A	p.Ala167Asp	missense	Exon 2 of 23	ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.68
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.096
Sift	Benign	0.083	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.37
MutPred		0.23		Gain of glycosylation at Y165 (P = 0.0144)
MVP		0.24
MPC		0.22
ClinPred		0.28	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.49
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1391945564; hg19: chr4-110384423;