rs7058353

chrX-72181764-C-AchrX-72181764-C-G

Variant summary

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

The NM_006223.4(PIN4):c.-22C>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 (28282 hom., 27016 hem., cov: 22)
  • Exomes 𝑓: 0.92 (317387 hom. 326155 hem.)
  • Failed GnomAD Quality Control
• Consequence: PIN4 NM_006223.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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=2.1783342E-6).
• BS2: High Homozygotes in GnomAd at 28290 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIN4	NM_006223.4	c.-22C>A		5_prime_UTR_variant	1/4	ENST00000373669.8
PIN4	NM_001170747.1	c.54C>A	p.Ser18Arg	missense_variant	1/4
PIN4	NR_033187.2	n.8C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN4	ENST00000373669.8	c.-22C>A		5_prime_UTR_variant	1/4	1	NM_006223.4	P1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 92180 AN: 110069 Hom.: 28290 Cov.: 22 AF XY: 0.831 AC XY: 26971 AN XY: 32449

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.894

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.852

GnomAD3 exomes AF: 0.863 AC: 156944 AN: 181775 Hom.: 43880 AF XY: 0.868 AC XY: 57621 AN XY: 66419

Gnomad AFR exome AF: 0.626

Gnomad AMR exome AF: 0.853

Gnomad ASJ exome AF: 0.911

Gnomad EAS exome AF: 0.534

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: 1003715 AN: 1086911 Hom.: 317387 Cov.: 30 AF XY: 0.918 AC XY: 326155 AN XY: 355225

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: 92210 AN: 110123 Hom.: 28282 Cov.: 22 AF XY: 0.831 AC XY: 27016 AN XY: 32513

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.961

Gnomad4 OTH AF: 0.852

Alfa AF: 0.931 Hom.: 68360

Bravo AF: 0.823

TwinsUK AF: 0.957 AC: 3548

ALSPAC AF: 0.953 AC: 2754

ESP6500AA AF: 0.631 AC: 2418

ESP6500EA AF: 0.963 AC: 6481

ExAC AF: 0.860 AC: 104411

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	1.1
Dann	Benign	0.59
DEOGEN2	Benign	0.042	T;.;.
FATHMM_MKL	Benign	0.0078	N
MetaRNN	Benign	0.0000022	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.64	N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.12
MutPred		0.30		Loss of phosphorylation at S18 (P = 0.0375);Loss of phosphorylation at S18 (P = 0.0375);Loss of phosphorylation at S18 (P = 0.0375);
MPC		0.12
ClinPred		0.0010	T
GERP RS		-4.8
gMVP		0.22

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: rs7058353; hg19: chrX-71401614; COSMIC: COSV54484409; COSMIC: COSV54484409;