10-119919501-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007190.4(SEC23IP):c.1930A>G(p.Lys644Glu) variant causes a missense change. The variant allele was found at a frequency of 0.683 in 1,612,424 control chromosomes in the GnomAD database, including 377,922 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.71 ( 38845 hom., cov: 31)

Exomes 𝑓: 0.68 ( 339077 hom. )

Consequence

SEC23IP
NM_007190.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.98

Publications

45 publications found

Variant links:

Genes affected

SEC23IP (HGNC:17018): (SEC23 interacting protein) This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

SEC23IP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.4852725E-7).

BP6

Variant 10-119919501-A-G is Benign according to our data. Variant chr10-119919501-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059313.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEC23IP	NM_007190.4	MANE Select	c.1930A>G	p.Lys644Glu	missense	Exon 11 of 19	NP_009121.1
SEC23IP	NM_001411070.1		c.1930A>G	p.Lys644Glu	missense	Exon 11 of 19	NP_001397999.1
SEC23IP	NR_037771.2		n.1450A>G		non_coding_transcript_exon	Exon 10 of 18

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.1930A>G	p.Lys644Glu	missense	Exon 11 of 19	ENSP00000358071.3
	SEC23IP	ENST00000705471.1		c.1930A>G	p.Lys644Glu	missense	Exon 11 of 19	ENSP00000516127.1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108193

AN:

151890

Hom.:

38798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.701

GnomAD2 exomes

AF:

0.715

AC:

179039

AN:

250552

AF XY:

0.713

show subpopulations

Gnomad AFR exome

AF:

0.784

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.725

Gnomad EAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.680

AC:

992523

AN:

1460416

Hom.:

339077

Cov.:

AF XY:

0.682

AC XY:

495472

AN XY:

726536

show subpopulations

African (AFR)

AF:

0.785

AC:

26240

AN:

33432

American (AMR)

AF:

0.757

AC:

33757

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

18736

AN:

26102

East Asian (EAS)

AF:

0.830

AC:

32914

AN:

39672

South Asian (SAS)

AF:

0.743

AC:

63984

AN:

86102

European-Finnish (FIN)

AF:

0.652

AC:

34765

AN:

53296

Middle Eastern (MID)

AF:

0.696

AC:

4006

AN:

5754

European-Non Finnish (NFE)

AF:

0.663

AC:

736556

AN:

1111126

Other (OTH)

AF:

0.689

AC:

41565

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15281

30562

45844

61125

76406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19228

38456

57684

76912

96140

<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:

0.712

AC:

108293

AN:

152008

Hom.:

38845

Cov.:

AF XY:

0.714

AC XY:

53091

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.784

AC:

32503

AN:

41446

American (AMR)

AF:

0.723

AC:

11062

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2476

AN:

3470

East Asian (EAS)

AF:

0.817

AC:

4235

AN:

5182

South Asian (SAS)

AF:

0.735

AC:

3541

AN:

4820

European-Finnish (FIN)

AF:

0.656

AC:

6908

AN:

10530

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45384

AN:

67958

Other (OTH)

AF:

0.701

AC:

1480

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.686

Hom.:

141058

Bravo

AF:

0.718

TwinsUK

AF:

0.668

AC:

2476

ALSPAC

AF:

0.659

AC:

2540

ESP6500AA

AF:

0.779

AC:

3432

ESP6500EA

AF:

0.672

AC:

5783

ExAC

AF:

0.716

AC:

86941

Asia WGS

AF:

0.745

AC:

2594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEC23IP-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.065

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.12

MetaRNN

Benign

6.5e-7

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

PhyloP100

4.0

PrimateAI

Benign

0.40

PROVEAN

Benign

1.4

REVEL

Benign

0.084

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.042

MPC

0.17

ClinPred

0.0065

GERP RS

5.2

Varity_R

0.15

gMVP

0.18

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over