NM_031471.6:c.1317G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_031471.6(FERMT3):​c.1317G>A​(p.Gln439Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,611,142 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 6 hom. )

Consequence

FERMT3
NM_031471.6 synonymous

Scores

2
2
11

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.29

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.006200701).
BP6
Variant 11-64220441-G-A is Benign according to our data. Variant chr11-64220441-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 522223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00171 (260/152338) while in subpopulation NFE AF = 0.00288 (196/68010). AF 95% confidence interval is 0.00255. There are 0 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FERMT3NM_031471.6 linkc.1317G>A p.Gln439Gln synonymous_variant Exon 12 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.1317G>A p.Gln439Gln synonymous_variant Exon 12 of 15 1 NM_031471.6 ENSP00000339950.5 Q86UX7-2

Frequencies

GnomAD3 genomes
AF:
0.00171
AC:
260
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00245
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00288
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00193
AC:
468
AN:
243076
AF XY:
0.00205
show subpopulations
Gnomad AFR exome
AF:
0.000526
Gnomad AMR exome
AF:
0.000673
Gnomad ASJ exome
AF:
0.000101
Gnomad EAS exome
AF:
0.0000559
Gnomad FIN exome
AF:
0.00347
Gnomad NFE exome
AF:
0.00274
Gnomad OTH exome
AF:
0.000841
GnomAD4 exome
AF:
0.00251
AC:
3660
AN:
1458804
Hom.:
6
Cov.:
33
AF XY:
0.00256
AC XY:
1860
AN XY:
725834
show subpopulations
African (AFR)
AF:
0.000179
AC:
6
AN:
33446
American (AMR)
AF:
0.000741
AC:
33
AN:
44526
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26100
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39688
South Asian (SAS)
AF:
0.00175
AC:
151
AN:
86228
European-Finnish (FIN)
AF:
0.00371
AC:
190
AN:
51244
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5766
European-Non Finnish (NFE)
AF:
0.00285
AC:
3170
AN:
1111484
Other (OTH)
AF:
0.00177
AC:
107
AN:
60322
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
219
438
656
875
1094
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
116
232
348
464
580
<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:
0.00171
AC:
260
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.00154
AC XY:
115
AN XY:
74478
show subpopulations
African (AFR)
AF:
0.000601
AC:
25
AN:
41576
American (AMR)
AF:
0.000653
AC:
10
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.000621
AC:
3
AN:
4834
European-Finnish (FIN)
AF:
0.00245
AC:
26
AN:
10632
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00288
AC:
196
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
12
24
36
48
60
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<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:
0.00176
Hom.:
0
Bravo
AF:
0.00148
TwinsUK
AF:
0.00135
AC:
5
ALSPAC
AF:
0.00208
AC:
8
ESP6500AA
AF:
0.000683
AC:
3
ESP6500EA
AF:
0.00210
AC:
18
ExAC
AF:
0.00201
AC:
244
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 3 Benign:3
Sep 06, 2017
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 01, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Oct 31, 2017
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.12
CADD
Benign
9.6
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0077
T
Eigen
Benign
0.029
Eigen_PC
Benign
0.022
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.24
T
MetaRNN
Benign
0.0062
T
MetaSVM
Benign
-0.76
T
PhyloP100
1.3
PROVEAN
Benign
0.53
N
REVEL
Benign
0.023
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
MVP
0.52
ClinPred
0.035
T
GERP RS
2.4
PromoterAI
-0.010
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Mutation Taster
=93/7
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs72920390; hg19: chr11-63987913; COSMIC: COSV54177839; COSMIC: COSV54177839; API