X-72181757-G-T

Variant names:

• chrX-72181757-G-T
• rs6525589
• NM_006223.4:c.-29G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170747.1(PIN4):​c.47G>T​(p.Arg16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PIN4 NM_001170747.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 23 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067880064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170747.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	NM_006223.4	MANE Select	c.-29G>T		5_prime_UTR	Exon 1 of 4	NP_006214.3
	PIN4	NM_001170747.1		c.47G>T	p.Arg16Leu	missense	Exon 1 of 4	NP_001164218.1	Q9Y237-3
	PIN4	NR_033187.2		n.1G>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	ENST00000373669.8	TSL:1 MANE Select	c.-29G>T		5_prime_UTR	Exon 1 of 4	ENSP00000362773.3	Q9Y237-1
	PIN4	ENST00000913143.1		c.-29G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000583202.1
	PIN4	ENST00000218432.10	TSL:2	c.-29G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000218432.6	J3KMW3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1086035 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 354281

African (AFR) AF: 0.00 AC: 0 AN: 26220

American (AMR) AF: 0.00 AC: 0 AN: 35098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19313

East Asian (EAS) AF: 0.00 AC: 0 AN: 30171

South Asian (SAS) AF: 0.00 AC: 0 AN: 53872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3206

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832017

Other (OTH) AF: 0.00 AC: 0 AN: 45634

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.039
DANN	Benign	0.54
DEOGEN2	Benign	0.044	T
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.0060
Sift	Benign	0.077	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.086
MutPred		0.44		Loss of solvent accessibility (P = 0.0299)
MVP		0.043
MPC		0.13
ClinPred		0.085	T
GERP RS		-2.0
PromoterAI		-0.046	Neutral
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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: rs6525589; hg19: chrX-71401607;