Genetic Variant SEC31B:p.Ala1169Ser (chr10-100487651-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015490.4(SEC31B):c.3505G>T(p.Ala1169Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,612,572 control chromosomes in the GnomAD database, including 40,335 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. A1169V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.21 ( 3605 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36730 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43

Publications

37 publications found

Variant links:

Genes affected

SEC31B (HGNC:23197): (SEC31 homolog B, COPII coat complex component) This gene encodes a protein of unknown function. The protein has moderate similarity to rat VAP1 protein which is an endosomal membrane-associated protein, containing a putative Ca2+/calmodulin-dependent kinase II phosphorylation site. [provided by RefSeq, Jul 2008]

SEC31B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021184087).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4 link	c.3505G>T	p.Ala1169Ser	missense_variant	Exon 26 of 26	ENST00000370345.8	NP_056305.1	Q9NQW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8 link	c.3505G>T	p.Ala1169Ser	missense_variant	Exon 26 of 26	1	NM_015490.4	ENSP00000359370.3		Q9NQW1-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32638

AN:

152060

Hom.:

3589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.207

GnomAD2 exomes

AF:

0.208

AC:

51577

AN:

248484

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.222

AC:

324418

AN:

1460394

Hom.:

36730

Cov.:

AF XY:

0.223

AC XY:

162112

AN XY:

726366

show subpopulations

African (AFR)

AF:

0.210

AC:

7028

AN:

33464

American (AMR)

AF:

0.161

AC:

7199

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5418

AN:

26114

East Asian (EAS)

AF:

0.156

AC:

6190

AN:

39680

South Asian (SAS)

AF:

0.231

AC:

19830

AN:

85992

European-Finnish (FIN)

AF:

0.234

AC:

12440

AN:

53192

Middle Eastern (MID)

AF:

0.213

AC:

1230

AN:

5764

European-Non Finnish (NFE)

AF:

0.227

AC:

251850

AN:

1111282

Other (OTH)

AF:

0.219

AC:

13233

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13622

27245

40867

54490

68112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8592

17184

25776

34368

42960

<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:

0.215

AC:

32677

AN:

152178

Hom.:

3605

Cov.:

AF XY:

0.214

AC XY:

15937

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.215

AC:

8916

AN:

41498

American (AMR)

AF:

0.184

AC:

2809

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

707

AN:

3470

East Asian (EAS)

AF:

0.129

AC:

669

AN:

5176

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2356

AN:

10584

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15424

AN:

68012

Other (OTH)

AF:

0.204

AC:

431

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1365

2731

4096

5462

6827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.221

Hom.:

12437

Bravo

AF:

0.212

TwinsUK

AF:

0.224

AC:

831

ALSPAC

AF:

0.220

AC:

846

ESP6500AA

AF:

0.206

AC:

908

ESP6500EA

AF:

0.227

AC:

1955

ExAC

AF:

0.211

AC:

25620

Asia WGS

AF:

0.193

AC:

669

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

3.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.075

Sift

Benign

0.22

Sift4G

Benign

0.19

Polyphen

0.012

Vest4

0.020

MPC

0.032

ClinPred

0.0080

GERP RS

1.2

Varity_R

0.031

gMVP

0.15

Mutation Taster

=94/6

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over