20-6075047-TTG-T

Position:

• chr20-6075047-TTG-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_017671.5(FERMT1):​c.*2124_*2125del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 142,154 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FERMT1 NM_017671.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.615

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1734/142154) while in subpopulation AFR AF= 0.0422 (1575/37302). AF 95% confidence interval is 0.0405. There are 20 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.*2124_*2125del		3_prime_UTR_variant	15/15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.*2124_*2125del		3_prime_UTR_variant	15/15		XP_024307703.1
FERMT1	XM_047440259.1	c.*2124_*2125del		3_prime_UTR_variant	15/15		XP_047296215.1
FERMT1	XM_047440260.1	c.*2124_*2125del		3_prime_UTR_variant	14/14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.*2124_*2125del		3_prime_UTR_variant	15/15	1	NM_017671.5	ENSP00000217289	P1
FERMT1	ENST00000478194.1	n.3118_3119del		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1735 AN: 142080 Hom.: 20 Cov.: 23

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000781

Gnomad SAS AF: 0.000441

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000276

Gnomad OTH AF: 0.0123

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 128 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72

Gnomad4 EAS exome AF: 0.00

GnomAD4 genome AF: 0.0122 AC: 1734 AN: 142154 Hom.: 20 Cov.: 23 AF XY: 0.0122 AC XY: 846 AN XY: 69320

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000783

Gnomad4 SAS AF: 0.000442

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000276

Gnomad4 OTH AF: 0.0122

Alfa AF: 0.0106 Hom.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kindler syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs886056892; hg19: chr20-6055694;