rs869312730

Variant names:

• chr20-6089053-A-C
• rs869312730
• NM_017671.5:c.1176T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-6089053-A-C
• chr20-6089053-A-T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_017671.5(FERMT1):​c.1176T>G​(p.Tyr392*) 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
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0840
• Publications: 2 publications found

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]

FERMT1 Gene-Disease associations (from GenCC):

• Kindler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017671.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT1	NM_017671.5	MANE Select	c.1176T>G	p.Tyr392*	stop_gained	Exon 10 of 15	NP_060141.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT1	ENST00000217289.9	TSL:1 MANE Select	c.1176T>G	p.Tyr392*	stop_gained	Exon 10 of 15	ENSP00000217289.4	Q9BQL6-1
	FERMT1	ENST00000478194.1	TSL:1	n.136T>G		non_coding_transcript_exon	Exon 2 of 7
	FERMT1	ENST00000536936.1	TSL:1	n.*678T>G		non_coding_transcript_exon	Exon 9 of 14	ENSP00000441063.2	G3V1L6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Kindler syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.084
Vest4		0.91
GERP RS		-1.1
Mutation Taster		=2/198	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs869312730; hg19: chr20-6069700;