Genetic Variant FKBP14:p.Leu125Leu (chr7-30019098-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_017946.4(FKBP14):c.375G>A(p.Leu125Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L125L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKBP14
NM_017946.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.776

Publications

1 publications found

Variant links:

Genes affected

FKBP14 (HGNC:18625): (FKBP prolyl isomerase 14) The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]

FKBP14 links:

FKBP14-AS1 (HGNC:40990): (FKBP14 antisense RNA 1)

FKBP14-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 7-30019098-C-T is Benign according to our data. Variant chr7-30019098-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1734649.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.776 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017946.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP14	NM_017946.4	MANE Select	c.375G>A	p.Leu125Leu	synonymous	Exon 3 of 4	NP_060416.1	Q9NWM8
FKBP14	NR_046478.2		n.661G>A		non_coding_transcript_exon	Exon 4 of 5
FKBP14	NR_046479.2		n.417G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.375G>A	p.Leu125Leu	synonymous	Exon 3 of 4	ENSP00000222803.5	Q9NWM8
FKBP14	ENST00000419018.1	TSL:1	n.*22G>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000406270.1	F8WBZ0
FKBP14	ENST00000419018.1	TSL:1	n.*22G>A		3_prime_UTR	Exon 2 of 3	ENSP00000406270.1	F8WBZ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710592

African (AFR)

AF:

0.00

AC:

AN:

30974

American (AMR)

AF:

0.00

AC:

AN:

35554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

37428

South Asian (SAS)

AF:

0.00

AC:

AN:

79892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102238

Other (OTH)

AF:

0.00

AC:

AN:

59068

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over