rs6525589

chrX-72181757-G-AchrX-72181757-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006223.4(PIN4):c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.84 (28283 hom., 27008 hem., cov: 23)
  • Exomes 𝑓: 0.92 (316946 hom. 325046 hem.)
  • Failed GnomAD Quality Control
• Consequence: PIN4 NM_006223.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9685785E-6).
• BS2: High Homozygotes in GnomAd at 28291 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIN4	NM_006223.4	c.-29G>A		5_prime_UTR_variant	1/4	ENST00000373669.8
PIN4	NM_001170747.1	c.47G>A	p.Arg16Gln	missense_variant	1/4
PIN4	NR_033187.2	n.1G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN4	ENST00000373669.8	c.-29G>A		5_prime_UTR_variant	1/4	1	NM_006223.4	P1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 92177 AN: 110095 Hom.: 28291 Cov.: 23 AF XY: 0.831 AC XY: 26962 AN XY: 32457

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

GnomAD3 exomes AF: 0.863 AC: 157113 AN: 181962 Hom.: 43884 AF XY: 0.868 AC XY: 57792 AN XY: 66614

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 SAS exome AF: 0.771

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

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.851

Gnomad4 ASJ exome AF: 0.914

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.939

Gnomad4 NFE exome AF: 0.961

Gnomad4 OTH exome AF: 0.890

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

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.961

Gnomad4 OTH AF: 0.852

Alfa AF: 0.929 Hom.: 84520

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
MetaRNN	Benign	0.0000020	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.10	N;N;N
REVEL	Benign	0.015
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.016
MPC		0.12
ClinPred		0.00037	T
GERP RS		-2.0
gMVP		0.17

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