4-109433976-C-T

Variant names:

• chr4-109433976-C-T
• rs1325709170
• NM_006323.5:c.107C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006323.5(SEC24B):​c.107C>T​(p.Ala36Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: SEC24B NM_006323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.382
• 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]

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.088030845).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.107C>T	p.Ala36Val	missense	Exon 1 of 24	NP_006314.2	O95487-1
	SEC24B	NM_001300813.3		c.107C>T	p.Ala36Val	missense	Exon 1 of 25	NP_001287742.1	O95487-3
	SEC24B	NM_001318085.2		c.107C>T	p.Ala36Val	missense	Exon 1 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.107C>T	p.Ala36Val	missense	Exon 1 of 24	ENSP00000265175.4	O95487-1
	SEC24B	ENST00000504968.6	TSL:1	c.107C>T	p.Ala36Val	missense	Exon 1 of 25	ENSP00000428564.1	O95487-3
	SEC24B	ENST00000399100.6	TSL:1	c.107C>T	p.Ala36Val	missense	Exon 1 of 23	ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150496 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000472 AC: 5 AN: 1060178 Hom.: 0 Cov.: 30 AF XY: 0.00000792 AC XY: 4 AN XY: 505056

African (AFR) AF: 0.00 AC: 0 AN: 21384

American (AMR) AF: 0.00 AC: 0 AN: 7118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12450

East Asian (EAS) AF: 0.00 AC: 0 AN: 23050

South Asian (SAS) AF: 0.0000848 AC: 2 AN: 23578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2736

European-Non Finnish (NFE) AF: 0.00000330 AC: 3 AN: 908500

Other (OTH) AF: 0.00 AC: 0 AN: 41076

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150496 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73432

African (AFR) AF: 0.00 AC: 0 AN: 41224

American (AMR) AF: 0.00 AC: 0 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67520

Other (OTH) AF: 0.00 AC: 0 AN: 2076

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.38
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.090
Sift	Benign	0.031	D
Sift4G	Benign	0.28	T
Vest4		0.090
MutPred		0.26		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.65
MPC		0.14
ClinPred		0.13	T
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.050
gMVP		0.052
Mutation Taster		=94/6	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: rs1325709170; hg19: chr4-110355132;