NM_012181.5:c.379C>G

Variant names:

• chr19-18539634-G-C
• rs750717633
• NM_012181.5:c.379C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012181.5(FKBP8):​c.379C>G​(p.Leu127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: FKBP8 NM_012181.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• Publications: 0 publications found

Genes affected

FKBP8 (HGNC:3724): (FKBP prolyl isomerase 8) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. Unlike the other members of the family, this encoded protein does not seem to have PPIase/rotamase activity. It may have a role in neurons associated with memory function. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012181.5. 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
	FKBP8	NM_012181.5	MANE Select	c.379C>G	p.Leu127Val	missense	Exon 3 of 9	NP_036313.3
	FKBP8	NM_001308373.2		c.379C>G	p.Leu127Val	missense	Exon 3 of 9	NP_001295302.1	Q14318-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP8	ENST00000608443.6	TSL:1 MANE Select	c.379C>G	p.Leu127Val	missense	Exon 3 of 9	ENSP00000476767.1	Q14318-2
	FKBP8	ENST00000222308.8	TSL:1	c.379C>G	p.Leu127Val	missense	Exon 3 of 9	ENSP00000222308.4	Q14318-1
	FKBP8	ENST00000544835.7	TSL:1	c.293-1861C>G		intron	N/A	ENSP00000441267.2	A0A0A0MTJ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249986 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.074
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.0040	B
Vest4		0.41
MutPred		0.73		Loss of sheet (P = 0.0817)
MVP		0.70
MPC		0.76
ClinPred		0.22	T
GERP RS		1.1
Varity_R		0.38
gMVP		0.65
Mutation Taster		=55/45	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: rs750717633; hg19: chr19-18650444;