chr11-64220630-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031471.6(FERMT3):c.1506C>T(p.Leu502Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,610,504 control chromosomes in the GnomAD database, including 24,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2479 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22422 hom. )

Consequence

FERMT3
NM_031471.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.38

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011279881).

BP6

Variant 11-64220630-C-T is Benign according to our data. Variant chr11-64220630-C-T is described in ClinVar as [Benign]. Clinvar id is 402864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64220630-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT3	NM_031471.6 link	c.1506C>T	p.Leu502Leu	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.1506C>T	p.Leu502Leu	synonymous_variant	Exon 12 of 15	1	NM_031471.6	ENSP00000339950.5		Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26416

AN:

152106

Hom.:

2473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.0887

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.179

AC:

43003

AN:

240268

Hom.:

4273

AF XY:

0.173

AC XY:

22722

AN XY:

131338

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.303

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.0974

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.172

AC:

250099

AN:

1458280

Hom.:

22422

Cov.:

AF XY:

0.169

AC XY:

122748

AN XY:

725280

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.0965

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.174

AC:

26448

AN:

152224

Hom.:

2479

Cov.:

AF XY:

0.175

AC XY:

13044

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.0890

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.168

Hom.:

947

Bravo

AF:

0.182

TwinsUK

AF:

0.172

AC:

639

ALSPAC

AF:

0.167

AC:

643

ESP6500AA

AF:

0.137

AC:

601

ESP6500EA

AF:

0.170

AC:

1457

ExAC

AF:

0.167

AC:

20227

Asia WGS

AF:

0.156

AC:

541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Leukocyte adhesion deficiency 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.94

DANN

Benign

0.90

DEOGEN2

Benign

0.018

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.1

REVEL

Benign

0.0090

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.055

ClinPred

0.010

GERP RS

-8.4

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

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