rs869312720

Positions:

• chr20-6115894-AGAC-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The ENST00000217289.9(FERMT1):​c.299_301del​(p.Arg100del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FERMT1 ENST00000217289.9 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000217289.9. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 20-6115894-AGAC-A is Pathogenic according to our data. Variant chr20-6115894-AGAC-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.299_301del	p.Arg100del	inframe_deletion	3/15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.299_301del	p.Arg100del	inframe_deletion	3/15		XP_024307703.1
FERMT1	XM_047440259.1	c.299_301del	p.Arg100del	inframe_deletion	3/15		XP_047296215.1
FERMT1	XM_047440260.1	c.14_16del	p.Arg5del	inframe_deletion	2/14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.299_301del	p.Arg100del	inframe_deletion	3/15	1	NM_017671.5	ENSP00000217289	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs869312720; hg19: chr20-6096541;