Variant 11-64211062-C-T 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 ENST00000345728.10(FERMT3):c.405C>T(p.His135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,596,214 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 125 hom. )

Consequence

FERMT3
ENST00000345728.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.390

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=-0.48).

BP6

Variant 11-64211062-C-T is Benign according to our data. Variant chr11-64211062-C-T is described in ClinVar as [Benign]. Clinvar id is 197359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64211062-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00921 (1402/152280) while in subpopulation NFE AF= 0.013 (884/68004). AF 95% confidence interval is 0.0123. There are 10 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT3	NM_031471.6 linkuse as main transcript	c.405C>T	p.His135=	synonymous_variant	4/15	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.405C>T	p.His135=	synonymous_variant	4/15	1	NM_031471.6	ENSP00000339950	P4	Q86UX7-2

Frequencies

GnomAD3 genomes

AF:

0.00920

AC:

1400

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00919

AC:

1948

AN:

211888

Hom.:

AF XY:

0.00886

AC XY:

1020

AN XY:

115088

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00838

Gnomad ASJ exome

AF:

0.0149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.0119

AC:

17247

AN:

1443934

Hom.:

125

Cov.:

AF XY:

0.0117

AC XY:

8394

AN XY:

716798

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00866

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00559

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00921

AC:

1402

AN:

152280

Hom.:

Cov.:

AF XY:

0.00915

AC XY:

681

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00884

Asia WGS

AF:

0.00144

AC:

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	FERMT3: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 05, 2015

- -

Leukocyte adhesion deficiency 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.4

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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