rs201144674

Variant names:

• chr7-73328624-G-A
• rs201144674
• NM_003602.5:c.107G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-73328624-G-A
• chr7-73328624-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003602.5(FKBP6):​c.107G>A​(p.Arg36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,610,476 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (11 hom.)
• Consequence: FKBP6 NM_003602.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005741358).
• BP6: Variant 7-73328624-G-A is Benign according to our data. Variant chr7-73328624-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3770716.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.107G>A	p.Arg36Gln	missense	Exon 2 of 9	NP_003593.3
	FKBP6	NM_001135211.3		c.92G>A	p.Arg31Gln	missense	Exon 2 of 9	NP_001128683.1	O75344-2
	FKBP6	NM_001281304.2		c.107G>A	p.Arg36Gln	missense	Exon 2 of 8	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.107G>A	p.Arg36Gln	missense	Exon 2 of 9	ENSP00000252037.4	O75344-1
	FKBP6	ENST00000429879.5	TSL:1	n.107G>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000403908.1	F8WD36
	FKBP6	ENST00000431982.6	TSL:2	c.92G>A	p.Arg31Gln	missense	Exon 2 of 9	ENSP00000416277.2	O75344-2

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 151864 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00427

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00672

GnomAD2 exomes AF: 0.00197 AC: 426 AN: 216660 AF XY: 0.00185

Gnomad AFR exome AF: 0.000168

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.000216

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000503

Gnomad NFE exome AF: 0.00255

Gnomad OTH exome AF: 0.00638

GnomAD4 exome AF: 0.00300 AC: 4372 AN: 1458494 Hom.: 11 Cov.: 30 AF XY: 0.00284 AC XY: 2064 AN XY: 725650

African (AFR) AF: 0.000419 AC: 14 AN: 33380

American (AMR) AF: 0.00472 AC: 211 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000105 AC: 9 AN: 86066

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53414

Middle Eastern (MID) AF: 0.00630 AC: 26 AN: 4130

European-Non Finnish (NFE) AF: 0.00346 AC: 3843 AN: 1110800

Other (OTH) AF: 0.00397 AC: 239 AN: 60174

GnomAD4 genome AF: 0.00191 AC: 290 AN: 151982 Hom.: 2 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74268

African (AFR) AF: 0.000627 AC: 26 AN: 41462

American (AMR) AF: 0.00426 AC: 65 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00256 AC: 174 AN: 67946

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00252

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00111 AC: 9

ExAC AF: 0.00156 AC: 186

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.027
Sift	Benign	0.46	T
Sift4G	Benign	0.39	T
Polyphen		0.091	B
Vest4		0.16
MVP		0.47
MPC		2.1
ClinPred		0.011	T
GERP RS		1.9
PromoterAI		-0.019	Neutral
Varity_R		0.069
gMVP		0.48
Mutation Taster		=95/5	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: rs201144674; hg19: chr7-72742627;