rs149000560

Positions:

chr11-64207494-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2

The NM_031471.6(FERMT3):c.130G>A(p.Gly44Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,613,364 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 80 hom. )

Consequence

FERMT3
NM_031471.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.32

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.011366427).

BP6

Variant 11-64207494-G-A is Benign according to our data. Variant chr11-64207494-G-A is described in ClinVar as [Benign]. Clinvar id is 195388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64207494-G-A is described in Lovd as [Likely_benign]. Variant chr11-64207494-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00566 (862/152236) while in subpopulation NFE AF= 0.00832 (566/68012). AF 95% confidence interval is 0.00775. There are 6 homozygotes in gnomad4. There are 397 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.130G>A	p.Gly44Arg	missense_variant	2/15	ENST00000345728.10	NP_113659.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT3	ENST00000345728.10 linkuse as main transcript	c.130G>A	p.Gly44Arg	missense_variant	2/15	1	NM_031471.6	ENSP00000339950	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

863

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00832

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00600

AC:

1501

AN:

250244

Hom.:

AF XY:

0.00607

AC XY:

821

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00807

Gnomad OTH exome

AF:

0.00967

GnomAD4 exome

AF:

0.00787

AC:

11493

AN:

1461128

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

5619

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00392

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.00853

Gnomad4 OTH exome

AF:

0.00845

GnomAD4 genome

AF:

0.00566

AC:

862

AN:

152236

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

397

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00832

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00952

Hom.:

Bravo

AF:

0.00625

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00966

AC:

ExAC

AF:

0.00568

AC:

689

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00795

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 28, 2015

- -

Leukocyte adhesion deficiency 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

FERMT3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;D;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.5

.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.87, 0.89

MutPred

0.90

Gain of MoRF binding (P = 0.0028);Gain of MoRF binding (P = 0.0028);Gain of MoRF binding (P = 0.0028);

MVP

0.79

MPC

1.3

ClinPred

0.019

GERP RS

4.5

Varity_R

0.87

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over