chr6-32129381-C-G

Variant names:

• chr6-32129381-C-G
• NM_022110.4:c.400G>C
• FKBPL p.Gly134Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022110.4(FKBPL):​c.400G>C​(p.Gly134Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBPL NM_022110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3023867).

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.400G>C	p.Gly134Arg	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.400G>C	p.Gly134Arg	missense	Exon 2 of 2	ENSP00000364298.3	Q9UIM3
	FKBPL	ENST00000887777.1		c.400G>C	p.Gly134Arg	missense	Exon 2 of 2	ENSP00000557836.1
	FKBPL	ENST00000930347.1		c.400G>C	p.Gly134Arg	missense	Exon 2 of 2	ENSP00000600406.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.042	D
Varity_R		0.17
gMVP		0.55
Mutation Taster		=83/17	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-32097158;