chr7-32957602-C-A

Variant names:

• chr7-32957602-C-A
• rs1025595247
• NM_007270.5:c.29C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007270.5(FKBP9):​c.29C>A​(p.Pro10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,475,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000098 (1 hom.)
• Consequence: FKBP9 NM_007270.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16082868).

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.29C>A	p.Pro10Gln	missense	Exon 1 of 10	NP_009201.2
	FKBP9	NM_001284341.2		c.29C>A	p.Pro10Gln	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.29C>A	p.Pro10Gln	missense	Exon 1 of 10	ENSP00000242209.4	O95302-1
	FKBP9	ENST00000538336.5	TSL:2	c.29C>A	p.Pro10Gln	missense	Exon 1 of 11	ENSP00000439250.1	O95302-3
	FKBP9	ENST00000875466.1		c.29C>A	p.Pro10Gln	missense	Exon 1 of 11	ENSP00000545525.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000135 AC: 1 AN: 74156 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000711

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000982 AC: 13 AN: 1323536 Hom.: 1 Cov.: 31 AF XY: 0.0000107 AC XY: 7 AN XY: 652106

African (AFR) AF: 0.000188 AC: 5 AN: 26590

American (AMR) AF: 0.0000782 AC: 2 AN: 25582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23166

East Asian (EAS) AF: 0.00 AC: 0 AN: 28618

South Asian (SAS) AF: 0.00 AC: 0 AN: 72730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4442

European-Non Finnish (NFE) AF: 0.00000379 AC: 4 AN: 1054346

Other (OTH) AF: 0.0000363 AC: 2 AN: 55032

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152170 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74338

African (AFR) AF: 0.000314 AC: 13 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000117

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	0.094
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.50
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.15	N
REVEL	Benign	0.015
Sift	Uncertain	0.029	D
Sift4G	Benign	0.38	T
Polyphen		0.026	B
Vest4		0.35
MutPred		0.38		Loss of glycosylation at P10 (P = 9e-04)
MVP		0.48
MPC		0.70
ClinPred		0.33	T
GERP RS		2.0
PromoterAI		-0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.037
gMVP		0.31
Mutation Taster		=87/13	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: rs1025595247; hg19: chr7-32997214;