4-109463252-C-T

Variant names:

• chr4-109463252-C-T
• rs374657201
• NM_006323.5:c.485C>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.485C>T​(p.Pro162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SEC24B NM_006323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2462165).
• BS2: High AC in GnomAdExome4 at 35 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.485C>T	p.Pro162Leu	missense	Exon 2 of 24	NP_006314.2	O95487-1
	SEC24B	NM_001300813.3		c.578C>T	p.Pro193Leu	missense	Exon 3 of 25	NP_001287742.1	O95487-3
	SEC24B	NM_001318085.2		c.485C>T	p.Pro162Leu	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.485C>T	p.Pro162Leu	missense	Exon 2 of 24	ENSP00000265175.4	O95487-1
	SEC24B	ENST00000504968.6	TSL:1	c.578C>T	p.Pro193Leu	missense	Exon 3 of 25	ENSP00000428564.1	O95487-3
	SEC24B	ENST00000399100.6	TSL:1	c.485C>T	p.Pro162Leu	missense	Exon 2 of 23	ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152152 Hom.: 0 Cov.: 32

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249542 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461822 Hom.: 0 Cov.: 35 AF XY: 0.0000193 AC XY: 14 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.11
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.065
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.6
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.042	D
Polyphen		0.57	P
Vest4		0.50
MutPred		0.36		Gain of helix (P = 0.0143)
MVP		0.56
MPC		0.35
ClinPred		0.79	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.28
Mutation Taster		=80/20	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: rs374657201; hg19: chr4-110384408;