Genetic Variant NM_022110.4:c.229_240dupTCTCATAAGTCT (chr6-32129540-G-GAGACTTATGAGA) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2

The NM_022110.4(FKBPL):c.229_240dupTCTCATAAGTCT(p.Ser80_His81insSerHisLysSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,614,196 control chromosomes in the GnomAD database, including 103 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0033 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 83 hom. )

Consequence

FKBPL
NM_022110.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.00100

Variant links:

Genes affected

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

FKBPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_022110.4.

BP6

Variant 6-32129540-G-GAGACTTATGAGA is Benign according to our data. Variant chr6-32129540-G-GAGACTTATGAGA is described in ClinVar as [Likely_benign]. Clinvar id is 3039678.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00327 (498/152308) while in subpopulation SAS AF= 0.0197 (95/4828). AF 95% confidence interval is 0.0165. There are 20 homozygotes in gnomad4. There are 242 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBPL	NM_022110.4 link	c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	ENST00000375156.4	NP_071393.2	Q9UIM3A0A024RCQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBPL	ENST00000375156.4 link	c.229_240dupTCTCATAAGTCT	p.Ser80_His81insSerHisLysSer	conservative_inframe_insertion	Exon 2 of 2	1	NM_022110.4	ENSP00000364298.3		Q9UIM3

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0117

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00704

AC:

1770

AN:

251452

Hom.:

AF XY:

0.00702

AC XY:

954

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0241

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00913

Gnomad SAS exome

AF:

0.0193

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000923

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00303

AC:

4430

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

2552

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00680

Gnomad4 SAS exome

AF:

0.0195

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000688

Gnomad4 OTH exome

AF:

0.00927

GnomAD4 genome

AF:

0.00327

AC:

498

AN:

152308

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00268

Hom.:

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FKBPL-related disorder

Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over