rs397509383

Positions:

• chr17-41820960-GCC-GA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_021939.4(FKBP10):​c.1271_1272delinsA​(p.Ala424AspfsTer12) variant causes a frameshift 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBP10 NM_021939.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.0720

Genes affected

FKBP10 (HGNC:18169): (FKBP prolyl isomerase 10) The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. This protein localizes to the endoplasmic reticulum and acts as a molecular chaperone. Alternatively spliced variants encoding different isoforms have been reported, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-41820961-CC-A is Pathogenic according to our data. Variant chr17-41820961-CC-A is described in ClinVar as [Pathogenic]. Clinvar id is 41425.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP10	NM_021939.4	c.1271_1272delinsA	p.Ala424AspfsTer12	frameshift_variant	8/10	ENST00000321562.9	NP_068758.3
FKBP10	XM_011525099.4	c.1328_1329delinsA	p.Ala443AspfsTer12	frameshift_variant	9/11		XP_011523401.1
FKBP10	XM_011525100.3	c.1055_1056delinsA	p.Ala352AspfsTer12	frameshift_variant	8/10		XP_011523402.1
FKBP10	XM_047436515.1	c.998_999delinsA	p.Ala333AspfsTer12	frameshift_variant	7/9		XP_047292471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP10	ENST00000321562.9	c.1271_1272delinsA	p.Ala424AspfsTer12	frameshift_variant	8/10	1	NM_021939.4	ENSP00000317232	P1

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: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Bruck syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2012

- -

Osteogenesis imperfecta type 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397509383; hg19: chr17-39977213;