chr7-32957595-C-T

Variant names:

• chr7-32957595-C-T
• rs1280574242
• NM_007270.5:c.22C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13726622).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007270.5. 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
	FKBP9	NM_007270.5	MANE Select	c.22C>T	p.Pro8Ser	missense	Exon 1 of 10	NP_009201.2
	FKBP9	NM_001284341.2		c.22C>T	p.Pro8Ser	missense	Exon 1 of 11	NP_001271270.1	O95302-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP9	ENST00000242209.9	TSL:1 MANE Select	c.22C>T	p.Pro8Ser	missense	Exon 1 of 10	ENSP00000242209.4	O95302-1
	FKBP9	ENST00000538336.5	TSL:2	c.22C>T	p.Pro8Ser	missense	Exon 1 of 11	ENSP00000439250.1	O95302-3
	FKBP9	ENST00000875466.1		c.22C>T	p.Pro8Ser	missense	Exon 1 of 11	ENSP00000545525.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26550

American (AMR) AF: 0.0000394 AC: 1 AN: 25396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23034

East Asian (EAS) AF: 0.00 AC: 0 AN: 28564

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053310

Other (OTH) AF: 0.00 AC: 0 AN: 54910

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.078
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.057
Sift	Benign	0.44	T
Sift4G	Uncertain	0.048	D
Polyphen		0.0	B
Vest4		0.20
MutPred		0.45		Loss of catalytic residue at P8 (P = 0.0172)
MVP		0.52
MPC		0.74
ClinPred		0.081	T
GERP RS		3.0
PromoterAI		-0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.031
gMVP		0.34
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1280574242; hg19: chr7-32997207;