7-73328618-G-T

Variant names:

• chr7-73328618-G-T
• rs782285165
• NM_003602.5:c.101G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003602.5(FKBP6):​c.101G>T​(p.Gly34Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKBP6 NM_003602.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP6	NM_003602.5	c.101G>T	p.Gly34Val	missense_variant	Exon 2 of 9	ENST00000252037.5	NP_003593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP6	ENST00000252037.5	c.101G>T	p.Gly34Val	missense_variant	Exon 2 of 9	1	NM_003602.5	ENSP00000252037.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000965 AC: 2 AN: 207248 Hom.: 0 AF XY: 0.00000881 AC XY: 1 AN XY: 113510

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	.;.;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.0	.;.;M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.8	D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.76
MutPred		0.42		.;.;Loss of disorder (P = 0.0478);Loss of disorder (P = 0.0478);
MVP		0.78
MPC		4.3
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.82
gMVP		0.87

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

LitVar

Other links and lift over

dbSNP: rs782285165; hg19: chr7-72742621;