11-64211102-GAGAAGA-GAGA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BS1_Supporting

The NM_031471.6(FERMT3):​c.456_458delGAA​(p.Lys153del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000155 in 1,571,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

FERMT3
NM_031471.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_031471.6
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000163 (231/1419526) while in subpopulation NFE AF= 0.000184 (201/1090032). AF 95% confidence interval is 0.000164. There are 0 homozygotes in gnomad4_exome. There are 109 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FERMT3NM_031471.6 linkc.456_458delGAA p.Lys153del disruptive_inframe_deletion Exon 4 of 15 ENST00000345728.10 NP_113659.3 Q86UX7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FERMT3ENST00000345728.10 linkc.456_458delGAA p.Lys153del disruptive_inframe_deletion Exon 4 of 15 1 NM_031471.6 ENSP00000339950.5 Q86UX7-2

Frequencies

GnomAD3 genomes
AF:
0.0000858
AC:
13
AN:
151528
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000728
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000113
AC:
20
AN:
176786
Hom.:
0
AF XY:
0.000116
AC XY:
11
AN XY:
94832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000367
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000151
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000179
Gnomad NFE exome
AF:
0.000196
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000163
AC:
231
AN:
1419526
Hom.:
0
AF XY:
0.000155
AC XY:
109
AN XY:
702474
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000259
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000810
Gnomad4 SAS exome
AF:
0.0000370
Gnomad4 FIN exome
AF:
0.000277
Gnomad4 NFE exome
AF:
0.000184
Gnomad4 OTH exome
AF:
0.000153
GnomAD4 genome
AF:
0.0000858
AC:
13
AN:
151528
Hom.:
0
Cov.:
32
AF XY:
0.000149
AC XY:
11
AN XY:
73948
show subpopulations
Gnomad4 AFR
AF:
0.0000728
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 3 Uncertain:1
Nov 27, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant, c.456_458del, results in the deletion of 1 amino acid(s) of the FERMT3 protein (p.Lys153del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs759155629, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FERMT3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs759155629; hg19: chr11-63978574; API