ENST00000864393.1:c.-207C>T – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The ENST00000864393.1(FKBP10):c.-207C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 657,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

FKBP10
ENST00000864393.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.481

Publications

0 publications found

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]

FKBP10 links:

P3H4 (HGNC:16946): (prolyl 3-hydroxylase family member 4 (inactive)) This nucleolar protein was first characterized because it was an autoantigen in cases on interstitial cystitis. The protein, with a predicted molecular weight of 50 kDa, appears to be localized in the particulate compartment of the interphase nucleolus, with a distribution distinct from that of nucleolar protein B23. During mitosis it is associated with chromosomes. [provided by RefSeq, Jul 2008]

P3H4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000499 (252/505416) while in subpopulation MID AF = 0.000929 (2/2152). AF 95% confidence interval is 0.000666. There are 0 homozygotes in GnomAdExome4. There are 152 alleles in the male GnomAdExome4 subpopulation. Median coverage is 6. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000864393.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP10	NM_021939.4	MANE Select	c.-207C>T		upstream_gene	N/A	NP_068758.3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
FKBP10	ENST00000864393.1	c.-207C>T	5_prime_UTR	Exon 1 of 11	ENSP00000534452.1
FKBP10	ENST00000864392.1	c.-207C>T	5_prime_UTR	Exon 1 of 10	ENSP00000534451.1
FKBP10	ENST00000914592.1	c.-207C>T	5_prime_UTR	Exon 1 of 8	ENSP00000584651.1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000499

AC:

252

AN:

505416

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

152

AN XY:

266820

show subpopulations

African (AFR)

AF:

0.000273

AC:

AN:

14674

American (AMR)

AF:

0.000214

AC:

AN:

28000

Ashkenazi Jewish (ASJ)

AF:

0.000516

AC:

AN:

15490

East Asian (EAS)

AF:

0.00

AC:

AN:

31054

South Asian (SAS)

AF:

0.000868

AC:

AN:

51814

European-Finnish (FIN)

AF:

0.0000676

AC:

AN:

29590

Middle Eastern (MID)

AF:

0.000929

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.000565

AC:

172

AN:

304608

Other (OTH)

AF:

0.000464

AC:

AN:

28034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000269

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41504

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

67988

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000277

Hom.:

Bravo

AF:

0.000348

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis imperfecta type 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.48

PromoterAI

0.23

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over