Variant rs11231726 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000279227.10(FERMT3):c.1080-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,613,730 control chromosomes in the GnomAD database, including 19,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.11 ( 1164 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17908 hom. )

Consequence

FERMT3
ENST00000279227.10 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0009682

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.280

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

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-64219867-C-T is Benign according to our data. Variant chr11-64219867-C-T is described in ClinVar as [Benign]. Clinvar id is 402863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.1080-24C>T		intron_variant		ENST00000345728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT3	ENST00000345728.10 linkuse as main transcript	c.1080-24C>T		intron_variant		1	NM_031471.6	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16842

AN:

152046

Hom.:

1164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0946

Gnomad SAS

AF:

0.0764

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.118

AC:

29489

AN:

250840

Hom.:

2003

AF XY:

0.119

AC XY:

16151

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0421

Gnomad AMR exome

AF:

0.0848

Gnomad ASJ exome

AF:

0.0715

Gnomad EAS exome

AF:

0.0870

Gnomad SAS exome

AF:

0.0724

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.151

AC:

221350

AN:

1461566

Hom.:

17908

Cov.:

AF XY:

0.149

AC XY:

108381

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0396

Gnomad4 AMR exome

AF:

0.0855

Gnomad4 ASJ exome

AF:

0.0709

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.0750

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.111

AC:

16849

AN:

152164

Hom.:

1164

Cov.:

AF XY:

0.108

AC XY:

8010

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0440

Gnomad4 AMR

AF:

0.0889

Gnomad4 ASJ

AF:

0.0761

Gnomad4 EAS

AF:

0.0944

Gnomad4 SAS

AF:

0.0769

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.0990

Alfa

AF:

0.125

Hom.:

312

Bravo

AF:

0.107

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.9

DANN

Benign

0.75

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00097

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.050

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