Genetic Variant SEC23IP:c.2026-42A>G (chr10-119920847-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007190.4(SEC23IP):c.2026-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,295,424 control chromosomes in the GnomAD database, including 5,537 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 430 hom., cov: 33)

Exomes 𝑓: 0.072 ( 5107 hom. )

Consequence

SEC23IP
NM_007190.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

6 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:

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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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23IP	NM_007190.4 link	c.2026-42A>G		intron_variant	Intron 11 of 18	ENST00000369075.8	NP_009121.1	Q9Y6Y8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8 link	c.2026-42A>G		intron_variant	Intron 11 of 18	1	NM_007190.4	ENSP00000358071.3		Q9Y6Y8-1
SEC23IP	ENST00000705471.1 link	c.2026-42A>G		intron_variant	Intron 11 of 18			ENSP00000516127.1		A0A994J542

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8330

AN:

152196

Hom.:

430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0368

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.0918

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0439

GnomAD2 exomes

AF:

0.0880

AC:

20105

AN:

228366

AF XY:

0.0959

show subpopulations

Gnomad AFR exome

AF:

0.00943

Gnomad AMR exome

AF:

0.0494

Gnomad ASJ exome

AF:

0.0453

Gnomad EAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.0918

Gnomad NFE exome

AF:

0.0555

Gnomad OTH exome

AF:

0.0742

GnomAD4 exome

AF:

0.0723

AC:

82639

AN:

1143110

Hom.:

5107

Cov.:

AF XY:

0.0784

AC XY:

45560

AN XY:

581382

show subpopulations

African (AFR)

AF:

0.00980

AC:

258

AN:

26324

American (AMR)

AF:

0.0455

AC:

1720

AN:

37794

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

947

AN:

23138

East Asian (EAS)

AF:

0.194

AC:

7316

AN:

37624

South Asian (SAS)

AF:

0.251

AC:

18485

AN:

73572

European-Finnish (FIN)

AF:

0.0880

AC:

4563

AN:

51840

Middle Eastern (MID)

AF:

0.0715

AC:

366

AN:

5116

European-Non Finnish (NFE)

AF:

0.0541

AC:

45352

AN:

838368

Other (OTH)

AF:

0.0736

AC:

3632

AN:

49334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3439

6878

10318

13757

17196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1610

3220

4830

6440

8050

<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:

0.0547

AC:

8336

AN:

152314

Hom.:

430

Cov.:

AF XY:

0.0601

AC XY:

4476

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0105

AC:

437

AN:

41594

American (AMR)

AF:

0.0370

AC:

566

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

960

AN:

5186

South Asian (SAS)

AF:

0.269

AC:

1297

AN:

4818

European-Finnish (FIN)

AF:

0.0918

AC:

973

AN:

10594

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0557

AC:

3788

AN:

68026

Other (OTH)

AF:

0.0454

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

388

776

1164

1552

1940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0347

Hom.:

Bravo

AF:

0.0441

Asia WGS

AF:

0.201

AC:

698

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0090

(source)

DANN

Benign

0.75

PhyloP100

-1.9

Mutation Taster

=100/0

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