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GeneBe

rs869312729

chr20-6089067-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_017671.5(FERMT1):c.1161del(p.Ala388LeufsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

FERMT1
NM_017671.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.437
Variant links:
Genes affected
FERMT1 (HGNC:15889): (FERM domain containing kindlin 1) This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
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 20-6089067-CT-C is Pathogenic according to our data. Variant chr20-6089067-CT-C is described in Lovd as [Pathogenic]. Variant chr20-6089067-CT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FERMT1NM_017671.5 linkuse as main transcriptc.1161del p.Ala388LeufsTer14 frameshift_variant 10/15 ENST00000217289.9
FERMT1XM_024451935.2 linkuse as main transcriptc.1161del p.Ala388LeufsTer14 frameshift_variant 10/15
FERMT1XM_047440259.1 linkuse as main transcriptc.1161del p.Ala388LeufsTer14 frameshift_variant 10/15
FERMT1XM_047440260.1 linkuse as main transcriptc.876del p.Ala293LeufsTer14 frameshift_variant 9/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FERMT1ENST00000217289.9 linkuse as main transcriptc.1161del p.Ala388LeufsTer14 frameshift_variant 10/151 NM_017671.5 P1Q9BQL6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1460148
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726406
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs869312729; hg19: chr20-6069714; API