Variant 11-64223417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_031471.6(FERMT3):c.1917G>A(p.Thr639=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,613,544 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 27 hom. )

Consequence

FERMT3
NM_031471.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-64223417-G-A is Benign according to our data. Variant chr11-64223417-G-A is described in ClinVar as [Benign]. Clinvar id is 194565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64223417-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00394 (600/152312) while in subpopulation NFE AF= 0.00444 (302/68026). AF 95% confidence interval is 0.00403. There are 3 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.1917G>A	p.Thr639=	synonymous_variant	15/15	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.1917G>A	p.Thr639=	synonymous_variant	15/15	1	NM_031471.6	ENSP00000339950	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00444

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00423

AC:

1060

AN:

250620

Hom.:

AF XY:

0.00428

AC XY:

580

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.000988

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00289

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00432

AC:

6314

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3082

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.00444

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.00394

AC:

600

AN:

152312

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.00444

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00278

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00539

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)

Apr 09, 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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.9

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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