rs776661768

Variant names:

• chr19-18539666-C-A
• rs776661768
• NM_012181.5:c.347G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-18539666-C-A
• chr19-18539666-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_012181.5(FKBP8):​c.347G>T​(p.Arg116Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000822 in 1,459,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R116C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: FKBP8 NM_012181.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.754
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP8	NM_012181.5	c.347G>T	p.Arg116Leu	missense_variant	Exon 3 of 9	ENST00000608443.6	NP_036313.3
FKBP8	NM_001308373.2	c.347G>T	p.Arg116Leu	missense_variant	Exon 3 of 9		NP_001295302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP8	ENST00000608443.6	c.347G>T	p.Arg116Leu	missense_variant	Exon 3 of 9	1	NM_012181.5	ENSP00000476767.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1459128 Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8 AN XY: 726036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000462 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	.;D;D;.;.;T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	.;.;D;D;D;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.012	T
MutationAssessor	Uncertain	2.0	M;M;M;M;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.2	.;.;D;.;.;.;.;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	.;.;D;.;.;.;.;.
Sift4G	Benign	0.23	T;T;T;T;.;T;.;.
Polyphen		0.82	P;P;P;P;.;.;.;.
Vest4		0.62
MutPred		0.54		Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);Gain of ubiquitination at K119 (P = 0.043);
MVP		0.76
MPC		1.8
ClinPred		0.98	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.76
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs776661768; hg19: chr19-18650476;