chr20-6075048-TG-T

Position:

• chr20-6075048-TG-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.*2124del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 137,926 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.012 (43 hom., cov: 23)
  • Exomes 𝑓: 0.0082 (0 hom.)
• Consequence: FERMT1 NM_017671.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13

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 = 0.0123 (1701/137804) while in subpopulation AFR AF= 0.0426 (1478/34660). AF 95% confidence interval is 0.0408. There are 43 homozygotes in gnomad4. There are 756 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 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.*2124del		3_prime_UTR_variant	15/15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.*2124del		3_prime_UTR_variant	15/15		XP_024307703.1
FERMT1	XM_047440259.1	c.*2124del		3_prime_UTR_variant	15/15		XP_047296215.1
FERMT1	XM_047440260.1	c.*2124del		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.*2124del		3_prime_UTR_variant	15/15	1	NM_017671.5	ENSP00000217289	P1
FERMT1	ENST00000478194.1	n.3118del		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1702 AN: 137726 Hom.: 43 Cov.: 23

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00509

Gnomad ASJ AF: 0.000607

Gnomad EAS AF: 0.00554

Gnomad SAS AF: 0.00179

Gnomad FIN AF: 0.000776

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00846

GnomAD4 exome AF: 0.00820 AC: 1 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0139 AC XY: 1 AN XY: 72

Gnomad4 EAS exome AF: 0.00820

GnomAD4 genome AF: 0.0123 AC: 1701 AN: 137804 Hom.: 43 Cov.: 23 AF XY: 0.0113 AC XY: 756 AN XY: 67060

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.00508

Gnomad4 ASJ AF: 0.000607

Gnomad4 EAS AF: 0.00555

Gnomad4 SAS AF: 0.00179

Gnomad4 FIN AF: 0.000776

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00839

Alfa AF: 0.000249 Hom.: 0

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: rs778361332; hg19: chr20-6055695; COSMIC: COSV54090374; COSMIC: COSV54090374;