X-72181781-C-G

Position:

• chrX-72181781-C-G

Variant summary

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

The NM_006223.4(PIN4):​c.-5C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,086,256 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: PIN4 NM_006223.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.113

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]

PIN4 (HGNC:):

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=0.097412825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN4	NM_006223.4	c.-5C>G		5_prime_UTR_premature_start_codon_gain_variant	1/4	ENST00000373669.8	NP_006214.3
PIN4	NM_006223.4	c.-5C>G		5_prime_UTR_variant	1/4	ENST00000373669.8	NP_006214.3
PIN4	NM_001170747.1	c.71C>G	p.Ser24Cys	missense_variant	1/4		NP_001164218.1
PIN4	NR_033187.2	n.25C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669	c.-5C>G		5_prime_UTR_premature_start_codon_gain_variant	1/4	1	NM_006223.4	ENSP00000362773.3
PIN4	ENST00000373669	c.-5C>G		5_prime_UTR_variant	1/4	1	NM_006223.4	ENSP00000362773.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1086256 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 352930

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: 0.00000240

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.71C>G (p.S24C) alteration is located in exon 1 (coding exon 1) of the PIN4 gene. This alteration results from a C to G substitution at nucleotide position 71, causing the serine (S) at amino acid position 24 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.67
DEOGEN2	Benign	0.064	T;.;.;T
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.54	.;T;T;.
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.65	N;N;N;N
REVEL	Benign	0.093
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.64	.;.;P;.
Vest4		0.17
MutPred		0.30		Gain of methylation at K25 (P = 0.0183);Gain of methylation at K25 (P = 0.0183);Gain of methylation at K25 (P = 0.0183);.;
MVP		0.068
MPC		0.16
ClinPred		0.26	T
GERP RS		-0.90
gMVP		0.24

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-71401631;