7-73330268-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_003602.5(FKBP6):​c.384C>T​(p.Pro128Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,614,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

FKBP6
NM_003602.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.03
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 Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 7-73330268-C-T is Benign according to our data. Variant chr7-73330268-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657550.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.03 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FKBP6NM_003602.5 linkuse as main transcriptc.384C>T p.Pro128Pro synonymous_variant 4/9 ENST00000252037.5 NP_003593.3 O75344-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FKBP6ENST00000252037.5 linkuse as main transcriptc.384C>T p.Pro128Pro synonymous_variant 4/91 NM_003602.5 ENSP00000252037.4 O75344-1

Frequencies

GnomAD3 genomes
AF:
0.000421
AC:
64
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000310
AC:
78
AN:
251492
Hom.:
0
AF XY:
0.000375
AC XY:
51
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000413
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000263
AC:
384
AN:
1461842
Hom.:
1
Cov.:
32
AF XY:
0.000283
AC XY:
206
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000402
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000452
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000245
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.000420
AC:
64
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.000443
AC XY:
33
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000366
Hom.:
0
Bravo
AF:
0.000608
EpiCase
AF:
0.000709
EpiControl
AF:
0.00101

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022FKBP6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
5.3
DANN
Benign
0.74

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: rs371618364; hg19: chr7-72744271; COSMIC: COSV52719456; COSMIC: COSV52719456; API