rs869312730

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_017671.5(FERMT1):​c.1176T>G​(p.Tyr392Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

FERMT1
NM_017671.5 stop_gained

Scores

2
1
4

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.0840
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 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FERMT1NM_017671.5 linkuse as main transcriptc.1176T>G p.Tyr392Ter stop_gained 10/15 ENST00000217289.9 NP_060141.3
FERMT1XM_024451935.2 linkuse as main transcriptc.1176T>G p.Tyr392Ter stop_gained 10/15 XP_024307703.1
FERMT1XM_047440259.1 linkuse as main transcriptc.1176T>G p.Tyr392Ter stop_gained 10/15 XP_047296215.1
FERMT1XM_047440260.1 linkuse as main transcriptc.891T>G p.Tyr297Ter stop_gained 9/14 XP_047296216.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FERMT1ENST00000217289.9 linkuse as main transcriptc.1176T>G p.Tyr392Ter stop_gained 10/151 NM_017671.5 ENSP00000217289 P1Q9BQL6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

Kindler syndrome Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.54
CADD
Pathogenic
32
DANN
Benign
0.95
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.55
FATHMM_MKL
Uncertain
0.89
D
MutationTaster
Benign
1.0
A;A
Vest4
0.91
GERP RS
-1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.28
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.28
Position offset: 36

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: rs869312730; hg19: chr20-6069700; API