dbSNP rs2295772: SEC31B:p.Pro372Ser (chr10-100505426-G-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.1114C>T(p.Pro372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,604,228 control chromosomes in the GnomAD database, including 38,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3385 hom., cov: 31)

Exomes 𝑓: 0.22 ( 34653 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

Publications

29 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:

ENSG00000255339 (HGNC:):

ENSG00000255339 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0035551488).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4 link	c.1114C>T	p.Pro372Ser	missense_variant	Exon 10 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.1114C>T	p.Pro372Ser	missense_variant	Exon 10 of 26	1	NM_015490.4	ENSP00000359370.3		Q9NQW1-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31458

AN:

151872

Hom.:

3377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.206

GnomAD2 exomes

AF:

0.206

AC:

49595

AN:

240672

AF XY:

0.208

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.216

AC:

313960

AN:

1452238

Hom.:

34653

Cov.:

AF XY:

0.217

AC XY:

156693

AN XY:

721820

show subpopulations

African (AFR)

AF:

0.193

AC:

6421

AN:

33212

American (AMR)

AF:

0.163

AC:

7153

AN:

44006

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5071

AN:

25472

East Asian (EAS)

AF:

0.177

AC:

6999

AN:

39432

South Asian (SAS)

AF:

0.228

AC:

19211

AN:

84212

European-Finnish (FIN)

AF:

0.233

AC:

12309

AN:

52890

Middle Eastern (MID)

AF:

0.217

AC:

1240

AN:

5726

European-Non Finnish (NFE)

AF:

0.219

AC:

242827

AN:

1107226

Other (OTH)

AF:

0.212

AC:

12729

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13138

26275

39413

52550

65688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8364

16728

25092

33456

41820

<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:

0.207

AC:

31475

AN:

151990

Hom.:

3385

Cov.:

AF XY:

0.208

AC XY:

15444

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.202

AC:

8368

AN:

41444

American (AMR)

AF:

0.180

AC:

2751

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3466

East Asian (EAS)

AF:

0.144

AC:

744

AN:

5184

South Asian (SAS)

AF:

0.230

AC:

1104

AN:

4810

European-Finnish (FIN)

AF:

0.221

AC:

2336

AN:

10564

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14814

AN:

67942

Other (OTH)

AF:

0.203

AC:

429

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1242

2484

3725

4967

6209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.212

Hom.:

2721

Bravo

AF:

0.204

TwinsUK

AF:

0.216

AC:

802

ALSPAC

AF:

0.214

AC:

824

ESP6500AA

AF:

0.195

AC:

858

ESP6500EA

AF:

0.220

AC:

1893

ExAC

AF:

0.208

AC:

25262

Asia WGS

AF:

0.192

AC:

666

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.3

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.00041

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.024

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PhyloP100

2.8

PrimateAI

Benign

0.32

PROVEAN

Benign

2.0

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.0050

MPC

0.033

ClinPred

0.0074

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.070

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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