7-32957715-C-A

Variant names:

• chr7-32957715-C-A
• NM_007270.5:c.142C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007270.5(FKBP9):​c.142C>A​(p.Pro48Thr) variant causes a missense 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FKBP9 NM_007270.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

Genes affected

FKBP9 (HGNC:3725): (FKBP prolyl isomerase 9) Predicted to enable calcium ion binding activity. Predicted to be involved in protein folding. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20438334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP9	NM_007270.5	c.142C>A	p.Pro48Thr	missense_variant	Exon 1 of 10	ENST00000242209.9	NP_009201.2
FKBP9	NM_001284341.2	c.142C>A	p.Pro48Thr	missense_variant	Exon 1 of 11		NP_001271270.1
FKBP9	XM_011515115.4	c.142C>A	p.Pro48Thr	missense_variant	Exon 1 of 7		XP_011513417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP9	ENST00000242209.9	c.142C>A	p.Pro48Thr	missense_variant	Exon 1 of 10	1	NM_007270.5	ENSP00000242209.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1379356 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682274

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142C>A (p.P48T) alteration is located in exon 1 (coding exon 1) of the FKBP9 gene. This alteration results from a C to A substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.0085	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.54	T;T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.50	N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.33
Sift	Benign	0.25	T;T
Sift4G	Uncertain	0.048	D;T
Polyphen		0.87	.;P
Vest4		0.21
MutPred		0.57		Gain of phosphorylation at P48 (P = 0.0612);Gain of phosphorylation at P48 (P = 0.0612);
MVP		0.86
MPC		1.3
ClinPred		0.62	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.20
gMVP		0.24

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: chr7-32997327;