NM_031471.6:c.1080-24C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031471.6(FERMT3):c.1080-24C>T variant causes a 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
NM_031471.6 intron

Scores

Splicing: ADA: 0.0009682

Clinical Significance

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

Conservation

PhyloP100: 0.280

Publications

12 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 VariationId 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 rank	MANE	Protein	UniProt
FERMT3	NM_031471.6 link	c.1080-24C>T		intron_variant	Intron 9 of 14	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.1080-24C>T		intron_variant	Intron 9 of 14	1	NM_031471.6	ENSP00000339950.5		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

GnomAD2 exomes

AF:

0.118

AC:

29489

AN:

250840

AF XY:

0.119

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 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

African (AFR)

AF:

0.0396

AC:

1327

AN:

33480

American (AMR)

AF:

0.0855

AC:

3826

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

1852

AN:

26134

East Asian (EAS)

AF:

0.126

AC:

4999

AN:

39696

South Asian (SAS)

AF:

0.0750

AC:

6469

AN:

86256

European-Finnish (FIN)

AF:

0.127

AC:

6742

AN:

53128

Middle Eastern (MID)

AF:

0.0586

AC:

338

AN:

5768

European-Non Finnish (NFE)

AF:

0.169

AC:

187910

AN:

1111990

Other (OTH)

AF:

0.131

AC:

7887

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13366

26732

40098

53464

66830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6638

13276

19914

26552

33190

<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:

0.111

AC:

16849

AN:

152164

Hom.:

1164

Cov.:

AF XY:

0.108

AC XY:

8010

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0440

AC:

1825

AN:

41520

American (AMR)

AF:

0.0889

AC:

1359

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3468

East Asian (EAS)

AF:

0.0944

AC:

488

AN:

5170

South Asian (SAS)

AF:

0.0769

AC:

371

AN:

4824

European-Finnish (FIN)

AF:

0.114

AC:

1205

AN:

10608

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10974

AN:

67966

Other (OTH)

AF:

0.0990

AC:

209

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

758

1516

2273

3031

3789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.123

Hom.:

314

Bravo

AF:

0.107

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.9

(source)

DANN

Benign

0.75

PhyloP100

0.28

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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