rs28732176

Variant names:

• chr6-32129513-C-T
• rs28732176
• NM_022110.4:c.268G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_022110.4(FKBPL):​c.268G>A​(p.Ala90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,614,130 control chromosomes in the GnomAD database, including 9,611 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8529 hom.)
• Consequence: FKBPL NM_022110.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.170
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013205111).
• BP6: Variant 6-32129513-C-T is Benign according to our data. Variant chr6-32129513-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060339.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022110.4. 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
	FKBPL	NM_022110.4	MANE Select	c.268G>A	p.Ala90Thr	missense	Exon 2 of 2	NP_071393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBPL	ENST00000375156.4	TSL:1 MANE Select	c.268G>A	p.Ala90Thr	missense	Exon 2 of 2	ENSP00000364298.3	Q9UIM3
	FKBPL	ENST00000887777.1		c.268G>A	p.Ala90Thr	missense	Exon 2 of 2	ENSP00000557836.1
	FKBPL	ENST00000930347.1		c.268G>A	p.Ala90Thr	missense	Exon 2 of 2	ENSP00000600406.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17183 AN: 152130 Hom.: 1087 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.0950 AC: 23876 AN: 251436 AF XY: 0.0981

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.0640

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0360

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.0973

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.103 AC: 149938 AN: 1461882 Hom.: 8529 Cov.: 34 AF XY: 0.103 AC XY: 74941 AN XY: 727240

African (AFR) AF: 0.168 AC: 5616 AN: 33480

American (AMR) AF: 0.0695 AC: 3107 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3441 AN: 26136

East Asian (EAS) AF: 0.0226 AC: 898 AN: 39700

South Asian (SAS) AF: 0.137 AC: 11804 AN: 86258

European-Finnish (FIN) AF: 0.0553 AC: 2956 AN: 53418

Middle Eastern (MID) AF: 0.0912 AC: 526 AN: 5768

European-Non Finnish (NFE) AF: 0.104 AC: 115162 AN: 1112002

Other (OTH) AF: 0.106 AC: 6428 AN: 60396

GnomAD4 genome AF: 0.113 AC: 17181 AN: 152248 Hom.: 1082 Cov.: 32 AF XY: 0.111 AC XY: 8234 AN XY: 74448

African (AFR) AF: 0.154 AC: 6393 AN: 41520

American (AMR) AF: 0.0800 AC: 1224 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3472

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5184

South Asian (SAS) AF: 0.157 AC: 755 AN: 4824

European-Finnish (FIN) AF: 0.0557 AC: 592 AN: 10620

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7159 AN: 68012

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.110 Hom.: 2040

Bravo AF: 0.117

TwinsUK AF: 0.0930 AC: 345

ALSPAC AF: 0.0999 AC: 385

ESP6500AA AF: 0.148 AC: 652

ESP6500EA AF: 0.110 AC: 942

ExAC AF: 0.0983 AC: 11930

Asia WGS AF: 0.0720 AC: 252 AN: 3478

EpiCase AF: 0.112

EpiControl AF: 0.105

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FKBPL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.17
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.16
Sift	Benign	0.20	T
Sift4G	Benign	0.35	T
Polyphen		0.0050	B
Vest4		0.026
MPC		0.41
ClinPred		0.0027	T
GERP RS		2.5
Varity_R		0.023
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

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: rs28732176; hg19: chr6-32097290; COSMIC: COSV64322917; COSMIC: COSV64322917;