rs869312721

Positions:

• chr20-6077337-CGAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The ENST00000217289.9(FERMT1):​c.1867_1869del​(p.Ile623del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 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: 0.0000021 (0 hom.)
• Consequence: FERMT1 ENST00000217289.9 inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.20

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 5 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 20-6077337-CGAT-C is Pathogenic according to our data. Variant chr20-6077337-CGAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 224168.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-6077337-CGAT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.1867_1869del	p.Ile623del	inframe_deletion	15/15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.1867_1869del	p.Ile623del	inframe_deletion	15/15		XP_024307703.1
FERMT1	XM_047440259.1	c.1867_1869del	p.Ile623del	inframe_deletion	15/15		XP_047296215.1
FERMT1	XM_047440260.1	c.1582_1584del	p.Ile528del	inframe_deletion	14/14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.1867_1869del	p.Ile623del	inframe_deletion	15/15	1	NM_017671.5	ENSP00000217289	P1
FERMT1	ENST00000478194.1	n.827_829del		non_coding_transcript_exon_variant	7/7	1
FERMT1	ENST00000536936.1	c.*1369_*1371del		3_prime_UTR_variant, NMD_transcript_variant	14/14	1		ENSP00000441063
FERMT1	ENST00000699095.1	c.1867_1869del	p.Ile623del	inframe_deletion	14/14			ENSP00000514127	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461856 Hom.: 0 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kindler syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Biomedical Innovation Departament, CIEMAT

Feb 08, 2010

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs869312721; hg19: chr20-6057984;