20-6075045-G-GTTT

Variant names:

• chr20-6075045-G-GTTT
• rs139990090
• ENST00000478194.1:n.3119_3121dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000478194.1(FERMT1):​n.3119_3121dupAAA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 133,104 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000075 (0 hom., cov: 31)
  • Exomes 𝑓: 0.016 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FERMT1 ENST00000478194.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 1 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.*2125_*2127dupAAA		3_prime_UTR_variant	Exon 15 of 15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.*2125_*2127dupAAA		3_prime_UTR_variant	Exon 15 of 15		XP_024307703.1
FERMT1	XM_047440259.1	c.*2125_*2127dupAAA		3_prime_UTR_variant	Exon 15 of 15		XP_047296215.1
FERMT1	XM_047440260.1	c.*2125_*2127dupAAA		3_prime_UTR_variant	Exon 14 of 14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000478194.1	n.3119_3121dupAAA		non_coding_transcript_exon_variant	Exon 7 of 7	1
FERMT1	ENST00000217289.9	c.*2125_*2127dupAAA		3_prime_UTR_variant	Exon 15 of 15	1	NM_017671.5	ENSP00000217289.4

Frequencies

GnomAD3 genomes AF: 0.00000751 AC: 1 AN: 133104 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000162

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0156 AC: 2 AN: 128 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0156 AC: 2 AN: 128

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00000751 AC: 1 AN: 133104 Hom.: 0 Cov.: 31 AF XY: 0.0000156 AC XY: 1 AN XY: 64242

African (AFR) AF: 0.00 AC: 0 AN: 35952

American (AMR) AF: 0.00 AC: 0 AN: 13036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3276

East Asian (EAS) AF: 0.00 AC: 0 AN: 4682

South Asian (SAS) AF: 0.00 AC: 0 AN: 4178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61712

Other (OTH) AF: 0.00 AC: 0 AN: 1850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139990090; hg19: chr20-6055692;