chr6-32129557-C-A

Variant names:

• chr6-32129557-C-A
• rs776870873
• NM_022110.4:c.224G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022110.4(FKBPL):​c.224G>T​(p.Gly75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,610,190 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: FKBPL NM_022110.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

Genes affected

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053187996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022110.4. 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
	FKBPL	NM_022110.4	MANE Select	c.224G>T	p.Gly75Val	missense	Exon 2 of 2	NP_071393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBPL	ENST00000375156.4	TSL:1 MANE Select	c.224G>T	p.Gly75Val	missense	Exon 2 of 2	ENSP00000364298.3	Q9UIM3
	FKBPL	ENST00000887777.1		c.224G>T	p.Gly75Val	missense	Exon 2 of 2	ENSP00000557836.1
	FKBPL	ENST00000930347.1		c.224G>T	p.Gly75Val	missense	Exon 2 of 2	ENSP00000600406.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151728 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000920 AC: 23 AN: 250072 AF XY: 0.0000962

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000648

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: 0.000164

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1458462 Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14 AN XY: 725488

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000548 AC: 24 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 85246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111240

Other (OTH) AF: 0.0000334 AC: 2 AN: 59894

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151728 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74084

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.0000661 AC: 1 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.000132 AC: 16

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	0.083
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		0.59	P
Vest4		0.26
MutPred		0.14		Gain of sheet (P = 0.0266)
MVP		0.98
MPC		1.2
ClinPred		0.13	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.40
Mutation Taster		=91/9	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: rs776870873; hg19: chr6-32097334;