7-73330159-T-G

Variant names:

• chr7-73330159-T-G
• NM_003602.5:c.275T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003602.5(FKBP6):​c.275T>G​(p.Leu92Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FKBP6 NM_003602.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68

Genes affected

FKBP6 (HGNC:3722): (FKBP prolyl isomerase family member 6 (inactive)) The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP6	NM_003602.5	c.275T>G	p.Leu92Arg	missense_variant	Exon 4 of 9	ENST00000252037.5	NP_003593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP6	ENST00000252037.5	c.275T>G	p.Leu92Arg	missense_variant	Exon 4 of 9	1	NM_003602.5	ENSP00000252037.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461090 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726890

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	.;.;.;D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.2	.;.;.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	D;D;T;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.96
MutPred		0.88		.;.;.;Gain of MoRF binding (P = 0.0017);
MVP		0.80
MPC		1.2
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.91
gMVP		0.97

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-72744162;