rs76744324
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_031471.6(FERMT3):c.1320G>A(p.Gln440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,611,164 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 45 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 44 hom. )
Consequence
FERMT3
NM_031471.6 synonymous
NM_031471.6 synonymous
Scores
2
1
12
Clinical Significance
Conservation
PhyloP100: 2.55
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.005191624).
BP6
Variant 11-64220444-G-A is Benign according to our data. Variant chr11-64220444-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.55 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1943/152340) while in subpopulation AFR AF= 0.0445 (1850/41564). AF 95% confidence interval is 0.0428. There are 45 homozygotes in gnomad4. There are 935 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 45 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FERMT3 | NM_031471.6 | c.1320G>A | p.Gln440= | synonymous_variant | 12/15 | ENST00000345728.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FERMT3 | ENST00000345728.10 | c.1320G>A | p.Gln440= | synonymous_variant | 12/15 | 1 | NM_031471.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0128 AC: 1943AN: 152222Hom.: 45 Cov.: 33
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GnomAD3 exomes AF: 0.00296 AC: 717AN: 242546Hom.: 18 AF XY: 0.00208 AC XY: 276AN XY: 132386
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GnomAD4 exome AF: 0.00125 AC: 1821AN: 1458824Hom.: 44 Cov.: 33 AF XY: 0.00105 AC XY: 761AN XY: 725814
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GnomAD4 genome AF: 0.0128 AC: 1943AN: 152340Hom.: 45 Cov.: 33 AF XY: 0.0126 AC XY: 935AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Leukocyte adhesion deficiency 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 17, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at