rs11415

chrX-72196871-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_006223.4(PIN4):c.204C>T(p.Ala68=) 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant X-72196871-C-T is Benign according to our data. Variant chrX-72196871-C-T is described in Lovd as [Likely_benign].
• 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/exons	MANE	UniProt
PIN4	NM_006223.4	c.204C>T	p.Ala68=	synonymous_variant	3/4	ENST00000373669.8
PIN4	NM_001170747.1	c.279C>T	p.Ala93=	synonymous_variant	3/4
PIN4	NR_033187.2	n.159C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN4	ENST00000373669.8	c.204C>T	p.Ala68=	synonymous_variant	3/4	1	NM_006223.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 14751 AN: 110830 Hom.: 1292 Cov.: 22 AF XY: 0.135 AC XY: 4466 AN XY: 33120

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

GnomAD3 exomes AF: 0.122 AC: 22080 AN: 181535 Hom.: 1911 AF XY: 0.114 AC XY: 7529 AN XY: 66177

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 SAS exome AF: 0.212

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

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.0607

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0971

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

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0664

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0570 Hom.: 1701

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11415; hg19: chrX-71416721; COSMIC: COSV54485488; COSMIC: COSV54485488;