rs11415

Variant names:

• chrX-72196871-C-T
• rs11415
• NM_006223.4:c.204C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006223.4(PIN4):​c.204C>T​(p.Ala68Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,201,062 control chromosomes in the GnomAD database, including 6,104 homozygotes. There are 30,213 hemizygotes in GnomAD. 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 0.13 (1291 hom., 4485 hem., cov: 22)
  • Exomes 𝑓: 0.068 (4813 hom. 25728 hem.)
• Consequence: PIN4 NM_006223.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 9 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.008).
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4	c.204C>T	p.Ala68Ala	synonymous_variant	Exon 3 of 4	ENST00000373669.8	NP_006214.3
PIN4	NM_001170747.1	c.279C>T	p.Ala93Ala	synonymous_variant	Exon 3 of 4		NP_001164218.1
PIN4	NR_033187.2	n.159C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8	c.204C>T	p.Ala68Ala	synonymous_variant	Exon 3 of 4	1	NM_006223.4	ENSP00000362773.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 14751 AN: 110830 Hom.: 1292 Cov.: 22

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.00436

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0720

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.122 AC: 22080 AN: 181535 AF XY: 0.114

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.0693

Gnomad EAS exome AF: 0.457

Gnomad FIN exome AF: 0.0619

Gnomad NFE exome AF: 0.0333

Gnomad OTH exome AF: 0.0841

GnomAD4 exome AF: 0.0679 AC: 74031 AN: 1090177 Hom.: 4813 Cov.: 27 AF XY: 0.0721 AC XY: 25728 AN XY: 356957

African (AFR) AF: 0.286 AC: 7466 AN: 26143

American (AMR) AF: 0.138 AC: 4824 AN: 35031

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 1262 AN: 19329

East Asian (EAS) AF: 0.475 AC: 14270 AN: 30062

South Asian (SAS) AF: 0.221 AC: 11834 AN: 53569

European-Finnish (FIN) AF: 0.0607 AC: 2458 AN: 40477

Middle Eastern (MID) AF: 0.0671 AC: 226 AN: 3370

European-Non Finnish (NFE) AF: 0.0326 AC: 27250 AN: 836457

Other (OTH) AF: 0.0971 AC: 4441 AN: 45739

GnomAD4 genome AF: 0.133 AC: 14772 AN: 110885 Hom.: 1291 Cov.: 22 AF XY: 0.135 AC XY: 4485 AN XY: 33183

African (AFR) AF: 0.280 AC: 8552 AN: 30491

American (AMR) AF: 0.139 AC: 1436 AN: 10351

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 175 AN: 2636

East Asian (EAS) AF: 0.479 AC: 1659 AN: 3464

South Asian (SAS) AF: 0.243 AC: 642 AN: 2644

European-Finnish (FIN) AF: 0.0555 AC: 328 AN: 5908

Middle Eastern (MID) AF: 0.0783 AC: 17 AN: 217

European-Non Finnish (NFE) AF: 0.0337 AC: 1783 AN: 52977

Other (OTH) AF: 0.117 AC: 177 AN: 1509

Alfa AF: 0.0576 Hom.: 1994

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11415; hg19: chrX-71416721; COSMIC: COSV54485488; COSMIC: COSV54485488;