Variant chr10-119933734-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007190.4(SEC23IP):c.2970A>G(p.Thr990Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,594,410 control chromosomes in the GnomAD database, including 6,289 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 ( 432 hom., cov: 33)

Exomes 𝑓: 0.069 ( 5857 hom. )

Consequence

SEC23IP
NM_007190.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.549

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:

SEC23IP (HGNC:):

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=-0.55).

BP6

Variant 10-119933734-A-G is Benign according to our data. Variant chr10-119933734-A-G is described in ClinVar as [Benign]. Clinvar id is 3056457.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.549 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.2970A>G	p.Thr990Thr	synonymous_variant	18/19	ENST00000369075.8	NP_009121.1	Q9Y6Y8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEC23IP	ENST00000369075.8 linkuse as main transcript	c.2970A>G	p.Thr990Thr	synonymous_variant	18/19	1	NM_007190.4	ENSP00000358071.3	Q9Y6Y8-1
SEC23IP	ENST00000705471.1 linkuse as main transcript	c.2967A>G	p.Thr989Thr	synonymous_variant	18/19			ENSP00000516127.1	A0A994J542
SEC23IP	ENST00000475542.1 linkuse as main transcript	n.516A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8330

AN:

152168

Hom.:

432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0368

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.0917

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0885

AC:

22192

AN:

250620

Hom.:

1713

AF XY:

0.0973

AC XY:

13187

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.0443

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.0922

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0711

GnomAD4 exome

AF:

0.0688

AC:

99230

AN:

1442124

Hom.:

5857

Cov.:

AF XY:

0.0748

AC XY:

53775

AN XY:

718684

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.0457

Gnomad4 ASJ exome

AF:

0.0402

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.0885

Gnomad4 NFE exome

AF:

0.0524

Gnomad4 OTH exome

AF:

0.0726

GnomAD4 genome

AF:

0.0547

AC:

8335

AN:

152286

Hom.:

432

Cov.:

AF XY:

0.0601

AC XY:

4473

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0369

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.0917

Gnomad4 NFE

AF:

0.0557

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0512

Hom.:

143

Bravo

AF:

0.0441

Asia WGS

AF:

0.201

AC:

700

AN:

3474

EpiCase

AF:

0.0563

EpiControl

AF:

0.0553

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

-0.55

CADD

Benign

7.2

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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