11-64220441-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_031471.6(FERMT3):c.1317G>A(p.Gln439Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,611,142 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 6 hom. )

Consequence

FERMT3
NM_031471.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.29

Publications

2 publications found

Variant links:

Genes affected

FERMT3 (HGNC:23151): (FERM domain containing kindlin 3) Kindlins are a small family of proteins that mediate protein-protein interactions involved in integrin activation and thereby have a role in cell adhesion, migration, differentiation, and proliferation. The protein encoded by this gene has a key role in the regulation of hemostasis and thrombosis. This protein may also help maintain the membrane skeleton of erythrocytes. Mutations in this gene cause the autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2010]

FERMT3 Gene-Disease associations (from GenCC):

leukocyte adhesion deficiency 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen

FERMT3 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 (MetaRNN=0.006200701).

BP6

Variant 11-64220441-G-A is Benign according to our data. Variant chr11-64220441-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 522223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00171 (260/152338) while in subpopulation NFE AF = 0.00288 (196/68010). AF 95% confidence interval is 0.00255. There are 0 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT3	NM_031471.6 link	c.1317G>A	p.Gln439Gln	synonymous_variant	Exon 12 of 15	ENST00000345728.10	NP_113659.3	Q86UX7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT3	ENST00000345728.10 link	c.1317G>A	p.Gln439Gln	synonymous_variant	Exon 12 of 15	1	NM_031471.6	ENSP00000339950.5		Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00193

AC:

468

AN:

243076

AF XY:

0.00205

show subpopulations

Gnomad AFR exome

AF:

0.000526

Gnomad AMR exome

AF:

0.000673

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.000841

GnomAD4 exome

AF:

0.00251

AC:

3660

AN:

1458804

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

1860

AN XY:

725834

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33446

American (AMR)

AF:

0.000741

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00175

AC:

151

AN:

86228

European-Finnish (FIN)

AF:

0.00371

AC:

190

AN:

51244

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00285

AC:

3170

AN:

1111484

Other (OTH)

AF:

0.00177

AC:

107

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

219

438

656

875

1094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152338

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41576

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00288

AC:

196

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00148

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00201

AC:

244

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 3

Benign:3

Sep 06, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Benign

9.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0077

Eigen

Benign

0.029

Eigen_PC

Benign

0.022

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.76

PhyloP100

1.3

PROVEAN

Benign

0.53

REVEL

Benign

0.023

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

MVP

0.52

ClinPred

0.035

GERP RS

2.4

PromoterAI

-0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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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