chr9-128343155-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005094.4(SLC27A4):c.28del(p.Val10CysfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC27A4
NM_005094.4 frameshift
NM_005094.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.551
Genes affected
SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-128343155-TG-T is Pathogenic according to our data. Variant chr9-128343155-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 2795966.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC27A4 | NM_005094.4 | c.28del | p.Val10CysfsTer9 | frameshift_variant | 2/13 | ENST00000300456.5 | |
SLC27A4 | XM_047422664.1 | c.61del | p.Val21CysfsTer9 | frameshift_variant | 2/13 | ||
SLC27A4 | XM_017014222.2 | c.28del | p.Val10CysfsTer9 | frameshift_variant | 3/14 | ||
SLC27A4 | XM_024447391.2 | c.28del | p.Val10CysfsTer9 | frameshift_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC27A4 | ENST00000300456.5 | c.28del | p.Val10CysfsTer9 | frameshift_variant | 2/13 | 1 | NM_005094.4 | P1 | |
SLC27A4 | ENST00000372870.5 | c.110del | p.Gly37ValfsTer50 | frameshift_variant | 2/6 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461594Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727108
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2023 | This variant has not been reported in the literature in individuals affected with SLC27A4-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val10Cysfs*9) in the SLC27A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC27A4 are known to be pathogenic (PMID: 19631310, 21450060). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.