NM_006223.4:c.-22C>A

Variant names:

• chrX-72181764-C-A
• rs7058353
• NM_006223.4:c.-22C>A

Variant summary

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

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
• Publications: 26 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=2.1783342E-6).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006223.4. 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
	PIN4	NM_006223.4	MANE Select	c.-22C>A		5_prime_UTR	Exon 1 of 4	NP_006214.3
	PIN4	NM_001170747.1		c.54C>A	p.Ser18Arg	missense	Exon 1 of 4	NP_001164218.1
	PIN4	NR_033187.2		n.8C>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	ENST00000373669.8	TSL:1 MANE Select	c.-22C>A		5_prime_UTR	Exon 1 of 4	ENSP00000362773.3
	PIN4	ENST00000664196.1		c.54C>A	p.Ser18Arg	missense	Exon 1 of 4	ENSP00000499466.1
	PIN4	ENST00000423432.6	TSL:2	c.54C>A	p.Ser18Arg	missense	Exon 1 of 4	ENSP00000409154.2

Frequencies

GnomAD3 genomes AF: 0.837 AC: 92180 AN: 110069 Hom.: 28290 Cov.: 22

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

GnomAD2 exomes AF: 0.863 AC: 156944 AN: 181775 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: 0.534

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

African (AFR) AF: 0.627 AC: 16384 AN: 26149

American (AMR) AF: 0.851 AC: 29823 AN: 35036

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 17647 AN: 19312

East Asian (EAS) AF: 0.526 AC: 15863 AN: 30131

South Asian (SAS) AF: 0.771 AC: 41471 AN: 53806

European-Finnish (FIN) AF: 0.939 AC: 38017 AN: 40502

Middle Eastern (MID) AF: 0.913 AC: 3011 AN: 3297

European-Non Finnish (NFE) AF: 0.961 AC: 800920 AN: 833059

Other (OTH) AF: 0.890 AC: 40579 AN: 45619

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

African (AFR) AF: 0.636 AC: 19200 AN: 30166

American (AMR) AF: 0.835 AC: 8664 AN: 10382

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 2388 AN: 2626

East Asian (EAS) AF: 0.517 AC: 1787 AN: 3457

South Asian (SAS) AF: 0.734 AC: 1897 AN: 2586

European-Finnish (FIN) AF: 0.943 AC: 5414 AN: 5744

Middle Eastern (MID) AF: 0.884 AC: 190 AN: 215

European-Non Finnish (NFE) AF: 0.961 AC: 50712 AN: 52764

Other (OTH) AF: 0.852 AC: 1279 AN: 1501

Alfa AF: 0.895 Hom.: 97330

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
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
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.76
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.30		Loss of phosphorylation at S18 (P = 0.0375)
MPC		0.12
ClinPred		0.0010	T
GERP RS		-4.8
PromoterAI		-0.0030	Neutral
gMVP		0.22
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: rs7058353; hg19: chrX-71401614; COSMIC: COSV54484409; COSMIC: COSV54484409;