7-73348420-T-C

Variant names:

• chr7-73348420-T-C
• rs12539763
• NM_003602.5:c.*2+5521T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003602.5(FKBP6):​c.*2+5521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,216 control chromosomes in the GnomAD database, including 1,317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1317 hom., cov: 32)
• Consequence: FKBP6 NM_003602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 4 publications found

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]

FKBP6 Gene-Disease associations (from GenCC):

• spermatogenic failure 77

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003602.5. 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
	FKBP6	NM_003602.5	MANE Select	c.*2+5521T>C		intron	N/A	NP_003593.3
	FKBP6	NM_001135211.3		c.*2+5521T>C		intron	N/A	NP_001128683.1	O75344-2
	FKBP6	NM_001281304.2		c.*2+5521T>C		intron	N/A	NP_001268233.1	O75344-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP6	ENST00000252037.5	TSL:1 MANE Select	c.*2+5521T>C		intron	N/A	ENSP00000252037.4	O75344-1
	FKBP6	ENST00000431982.6	TSL:2	c.*2+5521T>C		intron	N/A	ENSP00000416277.2	O75344-2
	FKBP6	ENST00000413573.6	TSL:5	c.*2+5521T>C		intron	N/A	ENSP00000394952.2	O75344-3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18985 AN: 152096 Hom.: 1317 Cov.: 32

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 18988 AN: 152216 Hom.: 1317 Cov.: 32 AF XY: 0.125 AC XY: 9320 AN XY: 74416

African (AFR) AF: 0.0899 AC: 3733 AN: 41542

American (AMR) AF: 0.0982 AC: 1501 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.146 AC: 756 AN: 5176

South Asian (SAS) AF: 0.126 AC: 609 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10596

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9756 AN: 68004

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.130 Hom.: 1413

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
PhyloP100		0.096

Splicing

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

Other links and lift over

dbSNP: rs12539763; hg19: chr7-72762429;