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5-134606988-C-CGTAA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_016103.4(SAR1B):c.558_559insTTAC(p.Gly187LeufsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SAR1B
NM_016103.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.0940
Variant links:
Genes affected
SAR1B (HGNC:10535): (secretion associated Ras related GTPase 1B) The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0653 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-134606988-C-CGTAA is Pathogenic according to our data. Variant chr5-134606988-C-CGTAA is described in ClinVar as [Pathogenic]. Clinvar id is 2926.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAR1BNM_016103.4 linkuse as main transcriptc.558_559insTTAC p.Gly187LeufsTer13 frameshift_variant 7/7 ENST00000402673.7
SAR1BNM_001033503.3 linkuse as main transcriptc.558_559insTTAC p.Gly187LeufsTer13 frameshift_variant 8/8
SAR1BXM_047417257.1 linkuse as main transcriptc.558_559insTTAC p.Gly187LeufsTer13 frameshift_variant 7/7
SAR1BXM_047417258.1 linkuse as main transcriptc.354_355insTTAC p.Gly119LeufsTer13 frameshift_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAR1BENST00000402673.7 linkuse as main transcriptc.558_559insTTAC p.Gly187LeufsTer13 frameshift_variant 7/71 NM_016103.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Chylomicron retention disease Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs1580645070; hg19: chr5-133942678; API