chr7-73340654-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003602.5(FKBP6):​c.605G>A​(p.Arg202His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,438 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0090 ( 30 hom., cov: 30)
Exomes 𝑓: 0.00089 ( 19 hom. )

Consequence

FKBP6
NM_003602.5 missense

Scores

18

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.377
Variant links:
Genes affected
FKBP6 (HGNC:3722): (FKBP prolyl isomerase family member 6 (inactive)) The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0029876232).
BP6
Variant 7-73340654-G-A is Benign according to our data. Variant chr7-73340654-G-A is described in ClinVar as [Benign]. Clinvar id is 3057196.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00897 (1363/152000) while in subpopulation AFR AF= 0.031 (1286/41446). AF 95% confidence interval is 0.0296. There are 30 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FKBP6NM_003602.5 linkuse as main transcriptc.605G>A p.Arg202His missense_variant 6/9 ENST00000252037.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FKBP6ENST00000252037.5 linkuse as main transcriptc.605G>A p.Arg202His missense_variant 6/91 NM_003602.5 P4O75344-1

Frequencies

GnomAD3 genomes
AF:
0.00884
AC:
1342
AN:
151882
Hom.:
26
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0306
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00342
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00623
GnomAD3 exomes
AF:
0.00230
AC:
573
AN:
249494
Hom.:
7
AF XY:
0.00191
AC XY:
258
AN XY:
135382
show subpopulations
Gnomad AFR exome
AF:
0.0291
Gnomad AMR exome
AF:
0.00180
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00228
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000707
Gnomad OTH exome
AF:
0.00148
GnomAD4 exome
AF:
0.000887
AC:
1296
AN:
1461438
Hom.:
19
Cov.:
37
AF XY:
0.000779
AC XY:
566
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.0296
Gnomad4 AMR exome
AF:
0.00210
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000655
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.00209
GnomAD4 genome
AF:
0.00897
AC:
1363
AN:
152000
Hom.:
30
Cov.:
30
AF XY:
0.00901
AC XY:
669
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0310
Gnomad4 AMR
AF:
0.00341
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00617
Alfa
AF:
0.00167
Hom.:
9
Bravo
AF:
0.0103
ESP6500AA
AF:
0.0267
AC:
105
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00261
AC:
316
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

FKBP6-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 01, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.21
DANN
Benign
0.85
DEOGEN2
Benign
0.052
.;.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0058
N
LIST_S2
Benign
0.34
T;T;T;T
MetaRNN
Benign
0.0030
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.6
.;.;.;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.54
N;N;N;N
REVEL
Benign
0.097
Sift
Benign
0.20
T;T;T;T
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.0
B;.;.;B
Vest4
0.10
MVP
0.74
MPC
0.37
ClinPred
0.0051
T
GERP RS
0.27
Varity_R
0.026
gMVP
0.074

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: rs142831087; hg19: chr7-72754656; API