chrX-72181764-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170747.1(PIN4):​c.54C>G​(p.Ser18Arg) 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. 12/16 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: 22)
• Consequence: PIN4 NM_001170747.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036812305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4	c.-22C>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000373669.8	NP_006214.3
PIN4	NM_001170747.1	c.54C>G	p.Ser18Arg	missense_variant	Exon 1 of 4		NP_001164218.1
PIN4	NR_033187.2	n.8C>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669	c.-22C>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_006223.4	ENSP00000362773.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.64	N;N;N
REVEL	Benign	0.0080
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.12
MutPred		0.30		Loss of phosphorylation at S18 (P = 0.0375);Loss of phosphorylation at S18 (P = 0.0375);Loss of phosphorylation at S18 (P = 0.0375);
MVP		0.043
MPC		0.12
ClinPred		0.015	T
GERP RS		-4.8
gMVP		0.22

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: rs7058353; hg19: chrX-71401614;