Genetic Variant NM_007190.4: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:

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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 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	Effect	Exon Rank	Protein	UniProt
SEC23IP	NM_007190.4	MANE Select	c.2026-42A>G	intron	N/A	NP_009121.1	Q9Y6Y8-1
SEC23IP	NM_001411070.1		c.2026-42A>G	intron	N/A	NP_001397999.1	A0A994J542
SEC23IP	NR_037771.2		n.1546-42A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23IP	ENST00000369075.8	TSL:1 MANE Select	c.2026-42A>G	intron	N/A	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000875162.1		c.2026-42A>G	intron	N/A	ENSP00000545221.1
SEC23IP	ENST00000970232.1		c.2026-42A>G	intron	N/A	ENSP00000640291.1

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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