Genetic Variant SEC24A:p.Ser285Asn (chr5-134674651-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021982.3(SEC24A):c.854G>A(p.Ser285Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,613,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

SEC24A
NM_021982.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.700

Publications

5 publications found

Variant links:

Genes affected

SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

SEC24A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018056244).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021982.3. 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
	SEC24A	NM_021982.3	MANE Select	c.854G>A	p.Ser285Asn	missense	Exon 5 of 23	NP_068817.1	O95486-1
	SEC24A	NM_001252231.2		c.854G>A	p.Ser285Asn	missense	Exon 5 of 13	NP_001239160.1	O95486-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC24A	ENST00000398844.7	TSL:2 MANE Select	c.854G>A	p.Ser285Asn	missense	Exon 5 of 23	ENSP00000381823.2	O95486-1
SEC24A	ENST00000322887.8	TSL:1	c.854G>A	p.Ser285Asn	missense	Exon 5 of 13	ENSP00000321749.4	O95486-2
SEC24A	ENST00000903398.1		c.974G>A	p.Ser325Asn	missense	Exon 6 of 24	ENSP00000573457.1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000329

AC:

AN:

249278

AF XY:

0.000348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000354

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000222

AC:

325

AN:

1461380

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33464

American (AMR)

AF:

0.000112

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000211

AC:

235

AN:

1111718

Other (OTH)

AF:

0.000315

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68034

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000596

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000730

AC:

ExAC

AF:

0.000323

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.030

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.72

M_CAP

Benign

0.0030

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.77

PhyloP100

0.70

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.70

REVEL

Benign

0.094

Sift

Benign

0.32

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.083

MVP

0.40

MPC

0.092

ClinPred

0.013

GERP RS

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.33

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over