chr11-64207523-C-G

Position:

chr11-64207523-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031471.6(FERMT3):c.159C>G(p.Ile53Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,602,188 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 10 hom. )

Consequence

FERMT3
NM_031471.6 missense, splice_region

Scores

Splicing: ADA: 0.1283

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.241

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050028563).

BP6

Variant 11-64207523-C-G is Benign according to our data. Variant chr11-64207523-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 195387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64207523-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00225 (343/152240) while in subpopulation NFE AF= 0.00404 (275/68006). AF 95% confidence interval is 0.00365. There are 1 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.159C>G	p.Ile53Met	missense_variant, splice_region_variant	2/15	ENST00000345728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT3	ENST00000345728.10 linkuse as main transcript	c.159C>G	p.Ile53Met	missense_variant, splice_region_variant	2/15	1	NM_031471.6	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00193

AC:

472

AN:

244656

Hom.:

AF XY:

0.00210

AC XY:

278

AN XY:

132442

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.000849

Gnomad ASJ exome

AF:

0.000852

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.00346

Gnomad OTH exome

AF:

0.00301

GnomAD4 exome

AF:

0.00320

AC:

4647

AN:

1449948

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

2226

AN XY:

719430

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.000744

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.00393

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152240

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00404

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.00227

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00185

AC:

225

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 08, 2015

- -

Leukocyte adhesion deficiency 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

FERMT3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.020

T;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.5

.;L;L

MutationTaster

Benign

0.92

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.058

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.079

T;T;T

Polyphen

0.031, 0.85

.;B;P

Vest4

0.26

MVP

0.65

MPC

0.39

ClinPred

0.013

GERP RS

4.5

Varity_R

0.13

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.13

dbscSNV1_RF

Benign

0.24

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

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