17-41817156-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_021939.4(FKBP10):​c.344G>T​(p.Arg115Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FKBP10
NM_021939.4 missense

Scores

10
7
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.87
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_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FKBP10NM_021939.4 linkc.344G>T p.Arg115Leu missense_variant Exon 2 of 10 ENST00000321562.9 NP_068758.3 Q96AY3-1A0A024R1W3Q8NAG5Q658U4
FKBP10XM_011525099.4 linkc.344G>T p.Arg115Leu missense_variant Exon 2 of 11 XP_011523401.1
FKBP10XM_011525100.3 linkc.119-933G>T intron_variant Intron 1 of 9 XP_011523402.1
FKBP10XM_047436515.1 linkc.119-933G>T intron_variant Intron 1 of 8 XP_047292471.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FKBP10ENST00000321562.9 linkc.344G>T p.Arg115Leu missense_variant Exon 2 of 10 1 NM_021939.4 ENSP00000317232.4 Q96AY3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461698
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727146
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
.;T;T;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.95
D;D;D;D
MetaSVM
Uncertain
0.78
D
MutationAssessor
Uncertain
2.7
.;.;.;M
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-6.6
.;.;D;D
REVEL
Pathogenic
0.92
Sift
Uncertain
0.0010
.;.;D;D
Sift4G
Uncertain
0.055
T;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
0.83
MutPred
0.82
.;Gain of methylation at R116 (P = 0.0917);.;Gain of methylation at R116 (P = 0.0917);
MVP
0.96
MPC
0.96
ClinPred
1.0
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39973408; API