chr6-32129644-G-C

Variant names:

• chr6-32129644-G-C
• rs35580488
• NM_022110.4:c.137C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_022110.4(FKBPL):​c.137C>G​(p.Thr46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,134 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0093 (9 hom., cov: 32)
  • Exomes 𝑓: 0.012 (108 hom.)
• Consequence: FKBPL NM_022110.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.112
• Publications: 8 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046557486).
• BP6: Variant 6-32129644-G-C is Benign according to our data. Variant chr6-32129644-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3041863.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 9 gene

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.137C>G	p.Thr46Arg	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.137C>G	p.Thr46Arg	missense	Exon 2 of 2	ENSP00000364298.3	Q9UIM3
	FKBPL	ENST00000887777.1		c.137C>G	p.Thr46Arg	missense	Exon 2 of 2	ENSP00000557836.1
	FKBPL	ENST00000930347.1		c.137C>G	p.Thr46Arg	missense	Exon 2 of 2	ENSP00000600406.1

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1415 AN: 152128 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0102 AC: 2562 AN: 251496 AF XY: 0.0104

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00679

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.00977

GnomAD4 exome AF: 0.0118 AC: 17276 AN: 1461888 Hom.: 108 Cov.: 33 AF XY: 0.0116 AC XY: 8450 AN XY: 727248

African (AFR) AF: 0.00161 AC: 54 AN: 33480

American (AMR) AF: 0.00680 AC: 304 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00206 AC: 178 AN: 86258

European-Finnish (FIN) AF: 0.0199 AC: 1061 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0135 AC: 15006 AN: 1112008

Other (OTH) AF: 0.0108 AC: 653 AN: 60396

GnomAD4 genome AF: 0.00929 AC: 1415 AN: 152246 Hom.: 9 Cov.: 32 AF XY: 0.00930 AC XY: 692 AN XY: 74434

African (AFR) AF: 0.00166 AC: 69 AN: 41558

American (AMR) AF: 0.0104 AC: 159 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.0208 AC: 221 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0137 AC: 931 AN: 68010

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00863 Hom.: 4

Bravo AF: 0.00835

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.0156 AC: 60

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0122 AC: 105

ExAC AF: 0.0103 AC: 1249

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0107

EpiControl AF: 0.0106

ClinVar

ClinVar submissions

Significance: Likely 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	0.080
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.5
DANN	Benign	0.97
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.11
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.050	D
Sift4G	Benign	0.21	T
Polyphen		0.26	B
Vest4		0.25
MPC		0.59
ClinPred		0.0066	T
GERP RS		1.8
Varity_R		0.062
gMVP		0.33
Mutation Taster		=100/0	polymorphism

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: rs35580488; hg19: chr6-32097421;