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GeneBe

rs17099368

chr10-119912139-T-C

Variant summary

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

The NM_007190.4(SEC23IP):c.1287T>C(p.Asp429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 1,613,904 control chromosomes in the GnomAD database, including 6,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.055 ( 431 hom., cov: 32)
Exomes 𝑓: 0.071 ( 6065 hom. )

Consequence

SEC23IP
NM_007190.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0180
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=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-119912139-T-C is Benign according to our data. Variant chr10-119912139-T-C is described in ClinVar as [Benign]. Clinvar id is 3055672.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=0.018 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 = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC23IPNM_007190.4 linkuse as main transcriptc.1287T>C p.Asp429= synonymous_variant 6/19 ENST00000369075.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC23IPENST00000369075.8 linkuse as main transcriptc.1287T>C p.Asp429= synonymous_variant 6/191 NM_007190.4 P4Q9Y6Y8-1
SEC23IPENST00000705471.1 linkuse as main transcriptc.1287T>C p.Asp429= synonymous_variant 6/19 A1
SEC23IPENST00000446561.1 linkuse as main transcriptc.399T>C p.Asp133= synonymous_variant 3/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0547
AC:
8317
AN:
152128
Hom.:
431
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0104
Gnomad AMI
AF:
0.0769
Gnomad AMR
AF:
0.0368
Gnomad ASJ
AF:
0.0378
Gnomad EAS
AF:
0.184
Gnomad SAS
AF:
0.269
Gnomad FIN
AF:
0.0916
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0557
Gnomad OTH
AF:
0.0435
GnomAD3 exomes
AF:
0.0889
AC:
22358
AN:
251358
Hom.:
1723
AF XY:
0.0977
AC XY:
13269
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.00947
Gnomad AMR exome
AF:
0.0490
Gnomad ASJ exome
AF:
0.0445
Gnomad EAS exome
AF:
0.187
Gnomad SAS exome
AF:
0.257
Gnomad FIN exome
AF:
0.0925
Gnomad NFE exome
AF:
0.0555
Gnomad OTH exome
AF:
0.0721
GnomAD4 exome
AF:
0.0705
AC:
103073
AN:
1461658
Hom.:
6065
Cov.:
31
AF XY:
0.0763
AC XY:
55508
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00956
Gnomad4 AMR exome
AF:
0.0461
Gnomad4 ASJ exome
AF:
0.0408
Gnomad4 EAS exome
AF:
0.195
Gnomad4 SAS exome
AF:
0.252
Gnomad4 FIN exome
AF:
0.0886
Gnomad4 NFE exome
AF:
0.0544
Gnomad4 OTH exome
AF:
0.0749
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0547
AC:
8323
AN:
152246
Hom.:
431
Cov.:
32
AF XY:
0.0600
AC XY:
4467
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0103
Gnomad4 AMR
AF:
0.0369
Gnomad4 ASJ
AF:
0.0378
Gnomad4 EAS
AF:
0.185
Gnomad4 SAS
AF:
0.270
Gnomad4 FIN
AF:
0.0916
Gnomad4 NFE
AF:
0.0557
Gnomad4 OTH
AF:
0.0449
Alfa
AF:
0.0512
Hom.:
199
Bravo
AF:
0.0441
Asia WGS
AF:
0.202
AC:
701
AN:
3478
EpiCase
AF:
0.0565
EpiControl
AF:
0.0555

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SEC23IP-related disorder 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
-0.64
Cadd
Benign
1.3
Dann
Benign
0.45
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.

Other links and lift over

dbSNP: rs17099368; hg19: chr10-121671651; COSMIC: COSV64831026; COSMIC: COSV64831026; API