6-35639794-T-T

Position:

• chr6-35639794-T-T

Variant summary

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

The NM_004117.4(FKBP5):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as drug response,risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: drug response; risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: 0.919

Genes affected

FKBP5 (HGNC:3721): (FKBP prolyl isomerase 5) 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. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

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
FKBP5	NM_004117.4	c.		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: drug response; risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

MAJOR DEPRESSIVE DISORDER, INCREASED RECURRENCE OF DEPRESSIVE EPISODES IN, SUSCEPTIBILITY TO Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2004

- -

Antidepressant drug treatment, accelerated response to Other:1

drug response, no assertion criteria provided

literature only

OMIM

Dec 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr6-35607571;