X-72181819-G-C

Variant names:

• chrX-72181819-G-C
• NM_006223.4:c.34G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006223.4(PIN4):​c.34G>C​(p.Ala12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000966 in 1,035,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.7e-7 (0 hom. 0 hem.)
• Consequence: PIN4 NM_006223.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11293253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4	c.34G>C	p.Ala12Pro	missense_variant	Exon 1 of 4	ENST00000373669.8	NP_006214.3
PIN4	NM_001170747.1	c.109G>C	p.Ala37Pro	missense_variant	Exon 1 of 4		NP_001164218.1
PIN4	NR_033187.2	n.63G>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8	c.34G>C	p.Ala12Pro	missense_variant	Exon 1 of 4	1	NM_006223.4	ENSP00000362773.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.66e-7 AC: 1 AN: 1035181 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 309727

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000127

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.064	T;.;.;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.34	.;T;T;.
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.83	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.063
Sift	Benign	0.074	T;D;T;D
Sift4G	Benign	0.096	T;T;T;T
Polyphen		0.12	.;.;B;.
Vest4		0.25
MutPred		0.18		Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);.;
MVP		0.27
MPC		0.17
ClinPred		0.30	T
GERP RS		4.2
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-71401669;