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GeneBe

17-41813050-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021939.4(FKBP10):c.16C>G(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,457,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P6P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FKBP10
NM_021939.4 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25
Variant links:
Genes affected
FKBP10 (HGNC:18169): (FKBP prolyl isomerase 10) The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. This protein localizes to the endoplasmic reticulum and acts as a molecular chaperone. Alternatively spliced variants encoding different isoforms have been reported, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057593256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FKBP10NM_021939.4 linkuse as main transcriptc.16C>G p.Pro6Ala missense_variant 1/10 ENST00000321562.9
FKBP10XM_011525099.4 linkuse as main transcriptc.16C>G p.Pro6Ala missense_variant 1/11
FKBP10XM_011525100.3 linkuse as main transcriptc.-112C>G 5_prime_UTR_variant 1/10
FKBP10XM_047436515.1 linkuse as main transcriptc.-112C>G 5_prime_UTR_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FKBP10ENST00000321562.9 linkuse as main transcriptc.16C>G p.Pro6Ala missense_variant 1/101 NM_021939.4 P1Q96AY3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000840
AC:
2
AN:
238018
Hom.:
0
AF XY:
0.00000763
AC XY:
1
AN XY:
131126
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000191
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1457856
Hom.:
0
Cov.:
31
AF XY:
0.0000276
AC XY:
20
AN XY:
725216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMar 25, 2022This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 6 of the FKBP10 protein (p.Pro6Ala). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FKBP10-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.61
Cadd
Benign
5.9
Dann
Benign
0.79
DEOGEN2
Benign
0.0092
T;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.52
T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
.;B
Vest4
0.13
MutPred
0.25
Loss of glycosylation at P6 (P = 0.0118);Loss of glycosylation at P6 (P = 0.0118);
MVP
0.51
MPC
0.25
ClinPred
0.020
T
GERP RS
0.30
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.018
gMVP
0.23

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: rs1555615647; hg19: chr17-39969302; API