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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.0880

AC:

20105

AN:

228366

Hom.:

1542

AF XY:

0.0959

AC XY:

11847

AN XY:

123498

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 SAS exome

AF:

0.262

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

Gnomad4 AFR exome

AF:

0.00980

Gnomad4 AMR exome

AF:

0.0455

Gnomad4 ASJ exome

AF:

0.0409

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.0880

Gnomad4 NFE exome

AF:

0.0541

Gnomad4 OTH exome

AF:

0.0736

GnomAD4 genome

AF:

0.0547

AC:

8336

AN:

152314

Hom.:

430

Cov.:

AF XY:

0.0601

AC XY:

4476

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.0918

Gnomad4 NFE

AF:

0.0557

Gnomad4 OTH

AF:

0.0454

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

DANN

Benign

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over