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GeneBe

rs34826964

chr10-119933734-A-G

Variant summary

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

The NM_007190.4(SEC23IP):c.2970A>G(p.Thr990=) 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 (★).

Frequency

Genomes: 𝑓 0.055 ( 432 hom., cov: 33)
Exomes 𝑓: 0.069 ( 5857 hom. )

Consequence

SEC23IP
NM_007190.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-119933734-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 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=0.549 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.2970A>G p.Thr990= synonymous_variant 18/19 ENST00000369075.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC23IPENST00000369075.8 linkuse as main transcriptc.2970A>G p.Thr990= synonymous_variant 18/191 NM_007190.4 P4Q9Y6Y8-1
SEC23IPENST00000705471.1 linkuse as main transcriptc.2967A>G p.Thr989= synonymous_variant 18/19 A1
SEC23IPENST00000475542.1 linkuse as main transcriptn.516A>G non_coding_transcript_exon_variant 4/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0547
AC:
8330
AN:
152168
Hom.:
432
Cov.:
33
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.:
27
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0547
AC:
8335
AN:
152286
Hom.:
432
Cov.:
33
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: 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
-0.55
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.

Other links and lift over

dbSNP: rs34826964; hg19: chr10-121693246; COSMIC: COSV64831058; API