20-6084063-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017671.5(FERMT1):c.1695T>C(p.Phe565Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,612,042 control chromosomes in the GnomAD database, including 110,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10836 hom., cov: 33)

Exomes 𝑓: 0.36 ( 99542 hom. )

Consequence

FERMT1
NM_017671.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.118

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 20-6084063-A-G is Benign according to our data. Variant chr20-6084063-A-G is described in ClinVar as [Benign]. Clinvar id is 260868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5 link	c.1695T>C	p.Phe565Phe	synonymous_variant	Exon 13 of 15	ENST00000217289.9	NP_060141.3	Q9BQL6-1Q54A15Q49AC8
FERMT1	XM_024451935.2 link	c.1695T>C	p.Phe565Phe	synonymous_variant	Exon 13 of 15		XP_024307703.1
FERMT1	XM_047440259.1 link	c.1695T>C	p.Phe565Phe	synonymous_variant	Exon 13 of 15		XP_047296215.1
FERMT1	XM_047440260.1 link	c.1410T>C	p.Phe470Phe	synonymous_variant	Exon 12 of 14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9 link	c.1695T>C	p.Phe565Phe	synonymous_variant	Exon 13 of 15	1	NM_017671.5	ENSP00000217289.4		Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56313

AN:

152038

Hom.:

10824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.387

GnomAD2 exomes

AF:

0.376

AC:

94290

AN:

250470

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.363

AC:

530625

AN:

1459886

Hom.:

99542

Cov.:

AF XY:

0.361

AC XY:

262202

AN XY:

726364

show subpopulations

African (AFR)

AF:

0.344

AC:

11518

AN:

33446

American (AMR)

AF:

0.482

AC:

21516

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9746

AN:

26128

East Asian (EAS)

AF:

0.636

AC:

25219

AN:

39662

South Asian (SAS)

AF:

0.275

AC:

23667

AN:

86180

European-Finnish (FIN)

AF:

0.274

AC:

14591

AN:

53344

Middle Eastern (MID)

AF:

0.372

AC:

2146

AN:

5764

European-Non Finnish (NFE)

AF:

0.360

AC:

399804

AN:

1110418

Other (OTH)

AF:

0.372

AC:

22418

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

17946

35893

53839

71786

89732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

56353

AN:

152156

Hom.:

10836

Cov.:

AF XY:

0.370

AC XY:

27486

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.350

AC:

14550

AN:

41516

American (AMR)

AF:

0.456

AC:

6969

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1285

AN:

3468

East Asian (EAS)

AF:

0.619

AC:

3195

AN:

5164

South Asian (SAS)

AF:

0.281

AC:

1357

AN:

4830

European-Finnish (FIN)

AF:

0.273

AC:

2887

AN:

10578

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24790

AN:

67998

Other (OTH)

AF:

0.393

AC:

827

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1836

3672

5509

7345

9181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.371

Hom.:

43373

Bravo

AF:

0.387

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.363

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kindler syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.2

(source)

DANN

Benign

0.65

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

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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20-6084063-A-G

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