rs6525589

Variant names:

• chrX-72181757-G-A
• rs6525589
• NM_006223.4:c.-29G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-72181757-G-A
• chrX-72181757-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001170747.1(PIN4):​c.47G>A​(p.Arg16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (28283 hom., 27008 hem., cov: 23)
  • Exomes 𝑓: 0.92 (316946 hom. 325046 hem.)
  • Failed GnomAD Quality Control
• Consequence: PIN4 NM_001170747.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 23 publications found

Genes affected

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9685785E-6).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170747.1. 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
	PIN4	NM_006223.4	MANE Select	c.-29G>A		5_prime_UTR	Exon 1 of 4	NP_006214.3
	PIN4	NM_001170747.1		c.47G>A	p.Arg16Gln	missense	Exon 1 of 4	NP_001164218.1	Q9Y237-3
	PIN4	NR_033187.2		n.1G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	ENST00000373669.8	TSL:1 MANE Select	c.-29G>A		5_prime_UTR	Exon 1 of 4	ENSP00000362773.3	Q9Y237-1
	PIN4	ENST00000664196.1		c.47G>A	p.Arg16Gln	missense	Exon 1 of 4	ENSP00000499466.1	Q9Y237-2
	PIN4	ENST00000423432.6	TSL:2	c.47G>A	p.Arg16Gln	missense	Exon 1 of 4	ENSP00000409154.2	Q9Y237-3

Frequencies

GnomAD3 genomes AF: 0.837 AC: 92177 AN: 110095 Hom.: 28291 Cov.: 23

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.894

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.851

GnomAD2 exomes AF: 0.863 AC: 157113 AN: 181962 AF XY: 0.868

Gnomad AFR exome AF: 0.626

Gnomad AMR exome AF: 0.853

Gnomad ASJ exome AF: 0.911

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.937

Gnomad NFE exome AF: 0.961

Gnomad OTH exome AF: 0.904

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.923 AC: 1001604 AN: 1084712 Hom.: 316946 Cov.: 28 AF XY: 0.918 AC XY: 325046 AN XY: 354140

African (AFR) AF: 0.627 AC: 16362 AN: 26116

American (AMR) AF: 0.851 AC: 29833 AN: 35051

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 17626 AN: 19286

East Asian (EAS) AF: 0.526 AC: 15861 AN: 30129

South Asian (SAS) AF: 0.771 AC: 41456 AN: 53789

European-Finnish (FIN) AF: 0.939 AC: 38017 AN: 40500

Middle Eastern (MID) AF: 0.913 AC: 2921 AN: 3201

European-Non Finnish (NFE) AF: 0.961 AC: 799014 AN: 831101

Other (OTH) AF: 0.890 AC: 40514 AN: 45539

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.837 AC: 92208 AN: 110150 Hom.: 28283 Cov.: 23 AF XY: 0.830 AC XY: 27008 AN XY: 32522

African (AFR) AF: 0.636 AC: 19205 AN: 30191

American (AMR) AF: 0.834 AC: 8644 AN: 10369

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 2389 AN: 2627

East Asian (EAS) AF: 0.517 AC: 1785 AN: 3453

South Asian (SAS) AF: 0.735 AC: 1915 AN: 2606

European-Finnish (FIN) AF: 0.943 AC: 5397 AN: 5726

Middle Eastern (MID) AF: 0.883 AC: 189 AN: 214

European-Non Finnish (NFE) AF: 0.961 AC: 50721 AN: 52775

Other (OTH) AF: 0.852 AC: 1283 AN: 1506

Alfa AF: 0.910 Hom.: 88386

Bravo AF: 0.823

TwinsUK AF: 0.957 AC: 3549

ALSPAC AF: 0.954 AC: 2756

ESP6500AA AF: 0.631 AC: 2418

ESP6500EA AF: 0.963 AC: 6480

ExAC AF: 0.860 AC: 104413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-1.1	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.038
DANN	Benign	0.83
DEOGEN2	Benign	0.043	T
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.015
Sift	Benign	1.0	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.12
ClinPred		0.00037	T
GERP RS		-2.0
PromoterAI		-0.029	Neutral
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs6525589; hg19: chrX-71401607; COSMIC: COSV54484467; COSMIC: COSV54484467;