7-73357128-T-C

Variant names:

• chr7-73357128-T-C
• rs17339199
• NM_003602.5:c.*3-1053T>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.*3-1053T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,212 control chromosomes in the GnomAD database, including 68,982 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 0.95 (68982 hom., cov: 30)
• Consequence: FKBP6 NM_003602.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP6	NM_003602.5	MANE Select	c.*3-1053T>C		intron	N/A	NP_003593.3
	FKBP6	NM_001135211.3		c.*3-1053T>C		intron	N/A	NP_001128683.1
	FKBP6	NM_001281304.2		c.*3-1053T>C		intron	N/A	NP_001268233.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP6	ENST00000252037.5	TSL:1 MANE Select	c.*3-1053T>C		intron	N/A	ENSP00000252037.4
	FKBP6	ENST00000431982.6	TSL:2	c.*3-1053T>C		intron	N/A	ENSP00000416277.2
	FKBP6	ENST00000413573.6	TSL:5	c.*3-1053T>C		intron	N/A	ENSP00000394952.2

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144707 AN: 152094 Hom.: 68926 Cov.: 30

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.951 AC: 144816 AN: 152212 Hom.: 68982 Cov.: 30 AF XY: 0.951 AC XY: 70767 AN XY: 74412

African (AFR) AF: 0.988 AC: 41033 AN: 41528

American (AMR) AF: 0.884 AC: 13513 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3339 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4708 AN: 5170

South Asian (SAS) AF: 0.988 AC: 4760 AN: 4818

European-Finnish (FIN) AF: 0.964 AC: 10222 AN: 10600

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64130 AN: 68022

Other (OTH) AF: 0.942 AC: 1993 AN: 2116

Alfa AF: 0.939 Hom.: 74356

Bravo AF: 0.943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs17339199; hg19: chr7-72771137;