Genetic Variant PFDN5:p.Ala147Val (chr12-53299320-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002624.4(PFDN5):c.440C>T(p.Ala147Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PFDN5
NM_002624.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

PFDN5 (HGNC:8869): (prefoldin subunit 5) This gene encodes a member of the prefoldin alpha subunit family. The encoded protein is one of six subunits of prefoldin, a molecular chaperone complex that binds and stabilizes newly synthesized polypeptides, thereby allowing them to fold correctly. The complex, consisting of two alpha and four beta subunits, forms a double beta barrel assembly with six protruding coiled-coils. The encoded protein may also repress the transcriptional activity of the proto-oncogene c-Myc. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PFDN5 links:

ENSG00000288663 (HGNC:):

ENSG00000288663 links:

MYG1-AS1 (HGNC:54810): (MYG1 antisense RNA 1)

MYG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17739382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN5	NM_002624.4 link	c.440C>T	p.Ala147Val	missense_variant	Exon 6 of 6	ENST00000334478.9	NP_002615.2	Q99471-1
PFDN5	NM_145897.3 link	c.305C>T	p.Ala102Val	missense_variant	Exon 4 of 4		NP_665904.1	Q99471-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN5	ENST00000334478.9 link	c.440C>T	p.Ala147Val	missense_variant	Exon 6 of 6	1	NM_002624.4	ENSP00000334188.4		Q99471-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250914

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135684

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459426

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726144

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440C>T (p.A147V) alteration is located in exon 6 (coding exon 6) of the PFDN5 gene. This alteration results from a C to T substitution at nucleotide position 440, causing the alanine (A) at amino acid position 147 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.;T

Eigen

Benign

0.014

Eigen_PC

Benign

0.097

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.92

.;D;D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.92

N;N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.021

D;D;D;D

Sift4G

Benign

0.088

T;T;T;T

Polyphen

0.75

P;.;.;P

Vest4

0.22

MutPred

0.29

Gain of loop (P = 0.0051);.;.;Gain of loop (P = 0.0051);

MVP

0.49

MPC

0.17

ClinPred

0.79

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over