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GeneBe

rs12771873

chr10-119926047-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_007190.4(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 (★).

Frequency

Genomes: 𝑓 0.055 ( 442 hom., cov: 33)
Exomes 𝑓: 0.071 ( 6116 hom. )

Consequence

SEC23IP
NM_007190.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.1 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
SEC23IPNM_007190.4 linkuse as main transcriptc.2133G>A p.Ala711= synonymous_variant 13/19 ENST00000369075.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC23IPENST00000369075.8 linkuse as main transcriptc.2133G>A p.Ala711= synonymous_variant 13/191 NM_007190.4 P4Q9Y6Y8-1
SEC23IPENST00000705471.1 linkuse as main transcriptc.2133G>A p.Ala711= synonymous_variant 13/19 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0552
AC:
8391
AN:
152058
Hom.:
442
Cov.:
33
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0552
AC:
8396
AN:
152176
Hom.:
442
Cov.:
33
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

SEC23IP-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This 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.

Other links and lift over

dbSNP: rs12771873; hg19: chr10-121685559; COSMIC: COSV64831051; COSMIC: COSV64831051; API