X-72181765-G-T

Variant names:

• chrX-72181765-G-T
• rs769563285
• NM_006223.4:c.-21G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001170747.1(PIN4):​c.55G>T​(p.Val19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,085,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 5 hem.)
• Consequence: PIN4 NM_001170747.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16680688).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

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.-21G>T		5_prime_UTR	Exon 1 of 4	NP_006214.3
	PIN4	NM_001170747.1		c.55G>T	p.Val19Phe	missense	Exon 1 of 4	NP_001164218.1	Q9Y237-3
	PIN4	NR_033187.2		n.9G>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.-21G>T		5_prime_UTR	Exon 1 of 4	ENSP00000362773.3	Q9Y237-1
	PIN4	ENST00000664196.1		c.55G>T	p.Val19Phe	missense	Exon 1 of 4	ENSP00000499466.1	Q9Y237-2
	PIN4	ENST00000423432.6	TSL:2	c.55G>T	p.Val19Phe	missense	Exon 1 of 4	ENSP00000409154.2	Q9Y237-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182439 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 14 AN: 1085604 Hom.: 0 Cov.: 27 AF XY: 0.0000142 AC XY: 5 AN XY: 352736

African (AFR) AF: 0.00 AC: 0 AN: 26232

American (AMR) AF: 0.00 AC: 0 AN: 35175

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19308

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 53789

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3359

European-Non Finnish (NFE) AF: 0.0000168 AC: 14 AN: 831411

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

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.4
DANN	Benign	0.97
DEOGEN2	Benign	0.056	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.73
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.045
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.77	P
Vest4		0.30
MutPred		0.25		Loss of catalytic residue at V19 (P = 0.136)
MVP		0.14
MPC		0.17
ClinPred		0.30	T
GERP RS		3.1
PromoterAI		-0.0019	Neutral
gMVP		0.36
Mutation Taster		=97/3	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: rs769563285; hg19: chrX-71401615;