Variant rs12771873 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000369075.8(SEC23IP):c.2133G>A(p.Ala711=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,609,484 control chromosomes in the GnomAD database, including 6,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.055 ( 442 hom., cov: 33)

Exomes 𝑓: 0.071 ( 6116 hom. )

Consequence

SEC23IP
ENST00000369075.8 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.10

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-119926047-G-A is Benign according to our data. Variant chr10-119926047-G-A is described in ClinVar as [Benign]. Clinvar id is 3055417.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23IP	NM_007190.4 linkuse as main transcript	c.2133G>A	p.Ala711=	synonymous_variant	13/19	ENST00000369075.8	NP_009121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23IP	ENST00000369075.8 linkuse as main transcript	c.2133G>A	p.Ala711=	synonymous_variant	13/19	1	NM_007190.4	ENSP00000358071	P4	Q9Y6Y8-1
SEC23IP	ENST00000705471.1 linkuse as main transcript	c.2133G>A	p.Ala711=	synonymous_variant	13/19			ENSP00000516127	A1

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8391

AN:

152058

Hom.:

442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.0914

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0900

AC:

22171

AN:

246450

Hom.:

1733

AF XY:

0.0985

AC XY:

13134

AN XY:

133368

show subpopulations

Gnomad AFR exome

AF:

0.00942

Gnomad AMR exome

AF:

0.0486

Gnomad ASJ exome

AF:

0.0449

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.0924

Gnomad NFE exome

AF:

0.0554

Gnomad OTH exome

AF:

0.0727

GnomAD4 exome

AF:

0.0708

AC:

103144

AN:

1457308

Hom.:

6116

Cov.:

AF XY:

0.0765

AC XY:

55458

AN XY:

724816

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.0455

Gnomad4 ASJ exome

AF:

0.0413

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.0887

Gnomad4 NFE exome

AF:

0.0544

Gnomad4 OTH exome

AF:

0.0755

GnomAD4 genome

AF:

0.0552

AC:

8396

AN:

152176

Hom.:

442

Cov.:

AF XY:

0.0606

AC XY:

4511

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0389

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.0914

Gnomad4 NFE

AF:

0.0557

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0513

Hom.:

319

Bravo

AF:

0.0446

Asia WGS

AF:

0.204

AC:

710

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEC23IP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.30

DANN

Benign

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over