chrX-72181764-C-G

Variant names:

• chrX-72181764-C-G
• rs7058353
• NM_006223.4:c.-22C>G

Variant summary

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

The ENST00000373669.8(PIN4):​c.-22C>G variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: PIN4 ENST00000373669.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 26 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=0.036812305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373669.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	NM_006223.4	MANE Select	c.-22C>G		5_prime_UTR	Exon 1 of 4	NP_006214.3
	PIN4	NM_001170747.1		c.54C>G	p.Ser18Arg	missense	Exon 1 of 4	NP_001164218.1
	PIN4	NR_033187.2		n.8C>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN4	ENST00000373669.8	TSL:1 MANE Select	c.-22C>G		5_prime_UTR	Exon 1 of 4	ENSP00000362773.3
	PIN4	ENST00000664196.1		c.54C>G	p.Ser18Arg	missense	Exon 1 of 4	ENSP00000499466.1
	PIN4	ENST00000423432.6	TSL:2	c.54C>G	p.Ser18Arg	missense	Exon 1 of 4	ENSP00000409154.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.2
DANN	Benign	0.42
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.76
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.30		Loss of phosphorylation at S18 (P = 0.0375)
MVP		0.043
MPC		0.12
ClinPred		0.015	T
GERP RS		-4.8
PromoterAI		-0.10	Neutral
gMVP		0.22
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: rs7058353; hg19: chrX-71401614;