Genetic Variant FERMT1:n.3117dupA (chr20-6075049-G-GT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_017671.5(FERMT1):c.*2123dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 129,034 control chromosomes in the GnomAD database, including 1,956 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.17 ( 1956 hom., cov: 22)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

FERMT1
NM_017671.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.184

Publications

0 publications found

Variant links:

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

FERMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5 link	c.*2123dupA	3_prime_UTR_variant	Exon 15 of 15	ENST00000217289.9	NP_060141.3	Q9BQL6-1Q54A15Q49AC8
FERMT1	XM_024451935.2 link	c.*2123dupA	3_prime_UTR_variant	Exon 15 of 15		XP_024307703.1
FERMT1	XM_047440259.1 link	c.*2123dupA	3_prime_UTR_variant	Exon 15 of 15		XP_047296215.1
FERMT1	XM_047440260.1 link	c.*2123dupA	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 link	n.3117dupA		non_coding_transcript_exon_variant	Exon 7 of 7	1
FERMT1	ENST00000217289.9 link	c.*2123dupA		3_prime_UTR_variant	Exon 15 of 15	1	NM_017671.5	ENSP00000217289.4		Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

21527

AN:

128952

Hom.:

1954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.00935

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.116

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.136

AC:

AN:

Hom.:

Cov.:

AF XY:

0.194

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.136

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.167

AC:

21532

AN:

128968

Hom.:

1956

Cov.:

AF XY:

0.168

AC XY:

10440

AN XY:

62024

show subpopulations

African (AFR)

AF:

0.101

AC:

3098

AN:

30786

American (AMR)

AF:

0.195

AC:

2637

AN:

13544

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

387

AN:

3102

East Asian (EAS)

AF:

0.00938

AC:

AN:

4692

South Asian (SAS)

AF:

0.129

AC:

542

AN:

4216

European-Finnish (FIN)

AF:

0.292

AC:

2079

AN:

7124

Middle Eastern (MID)

AF:

0.119

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.197

AC:

12340

AN:

62642

Other (OTH)

AF:

0.136

AC:

242

AN:

1778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

776

1552

2329

3105

3881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Kindler syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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20-6075049-G-GT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over