17-41813049-C-G

Variant names:

• chr17-41813049-C-G
• rs782670466
• NM_021939.4:c.15C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021939.4(FKBP10):​c.15C>G​(p.Gly5Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FKBP10 NM_021939.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 0 publications found

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]

FKBP10 Gene-Disease associations (from GenCC):

• Bruck syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• osteogenesis imperfecta type 11

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arthrogryposis-like syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Bruck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.458 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021939.4. 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
	FKBP10	NM_021939.4	MANE Select	c.15C>G	p.Gly5Gly	synonymous	Exon 1 of 10	NP_068758.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP10	ENST00000321562.9	TSL:1 MANE Select	c.15C>G	p.Gly5Gly	synonymous	Exon 1 of 10	ENSP00000317232.4	Q96AY3-1
	FKBP10	ENST00000914601.1		c.15C>G	p.Gly5Gly	synonymous	Exon 1 of 11	ENSP00000584660.1
	FKBP10	ENST00000864398.1		c.15C>G	p.Gly5Gly	synonymous	Exon 1 of 12	ENSP00000534457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457094 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724820

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4212

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111314

Other (OTH) AF: 0.0000166 AC: 1 AN: 60110

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.46
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs782670466; hg19: chr17-39969301;