7-32957595-C-T

Variant names:

• chr7-32957595-C-T
• NM_007270.5:c.22C>T

Variant summary

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

The NM_007270.5(FKBP9):​c.22C>T​(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FKBP9 NM_007270.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0780

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=0.13726622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP9	NM_007270.5	c.22C>T	p.Pro8Ser	missense_variant	Exon 1 of 10	ENST00000242209.9	NP_009201.2
FKBP9	NM_001284341.2	c.22C>T	p.Pro8Ser	missense_variant	Exon 1 of 11		NP_001271270.1
FKBP9	XM_011515115.4	c.22C>T	p.Pro8Ser	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.22C>T	p.Pro8Ser	missense_variant	Exon 1 of 10	1	NM_007270.5	ENSP00000242209.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1321242 Hom.: 0 Cov.: 31 AF XY: 0.00000307 AC XY: 2 AN XY: 650882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000394

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000138

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

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.22C>T (p.P8S) alteration is located in exon 1 (coding exon 1) of the FKBP9 gene. This alteration results from a C to T substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by a serine (S). 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	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.48	T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.35	N;N
REVEL	Benign	0.057
Sift	Benign	0.44	T;T
Sift4G	Uncertain	0.048	D;T
Polyphen		0.0	.;B
Vest4		0.20
MutPred		0.45		Loss of catalytic residue at P8 (P = 0.0172);Loss of catalytic residue at P8 (P = 0.0172);
MVP		0.52
MPC		0.74
ClinPred		0.081	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.031
gMVP		0.34

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: chr7-32997207;