20-1372153-C-T

Position:

• chr20-1372153-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000801.5(FKBP1A):​c.286G>A​(p.Ala96Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FKBP1A NM_000801.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.73

Genes affected

FKBP1A (HGNC:3711): (FKBP prolyl isomerase 1A) 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. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]

SDCBP2-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP1A	NM_000801.5	c.286G>A	p.Ala96Thr	missense_variant	4/5	ENST00000400137.9	NP_000792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1A	ENST00000400137.9	c.286G>A	p.Ala96Thr	missense_variant	4/5	1	NM_000801.5	ENSP00000383003.4
ENSG00000274322	ENST00000617804.1	n.204+19450G>A		intron_variant		4		ENSP00000479180.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.286G>A (p.A96T) alteration is located in exon 4 (coding exon 4) of the FKBP1A gene. This alteration results from a G to A substitution at nucleotide position 286, causing the alanine (A) at amino acid position 96 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.095	.;T;T;.;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	.;D;.;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.51	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.059	T;T;D;T;D
Sift4G	Uncertain	0.035	D;T;D;D;D
Polyphen		1.0	D;P;.;D;.
Vest4		0.73
MutPred		0.67		Loss of sheet (P = 0.0315);.;.;Loss of sheet (P = 0.0315);.;
MVP		0.72
MPC		2.5
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.42
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1352797;