Variant 20-54214351-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002623.4(PFDN4):c.25G>C(p.Ala9Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PFDN4
NM_002623.4 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.41

Variant links:

Genes affected

PFDN4 (HGNC:8868): (prefoldin subunit 4) This gene encodes a member of the prefoldin beta 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. [provided by RefSeq, Jul 2008]

PFDN4 links:

PFDN4 (HGNC:):

PFDN4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFDN4	NM_002623.4 linkuse as main transcript	c.25G>C	p.Ala9Pro	missense_variant, splice_region_variant	2/4	ENST00000371419.7	NP_002614.2	Q9NQP4
PFDN4	XM_047440198.1 linkuse as main transcript	c.271G>C	p.Ala91Pro	missense_variant, splice_region_variant	2/4		XP_047296154.1
PFDN4	XM_017027879.2 linkuse as main transcript	c.166G>C	p.Ala56Pro	missense_variant, splice_region_variant	2/4		XP_016883368.1
PFDN4	XM_047440199.1 linkuse as main transcript	c.271G>C	p.Ala91Pro	missense_variant, splice_region_variant	2/3		XP_047296155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFDN4	ENST00000371419.7 linkuse as main transcript	c.25G>C	p.Ala9Pro	missense_variant, splice_region_variant	2/4	1	NM_002623.4	ENSP00000360473.2		Q9NQP4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1387332

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

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:

9.45e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.0000555

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

The c.25G>C (p.A9P) alteration is located in exon 2 (coding exon 2) of the PFDN4 gene. This alteration results from a G to C substitution at nucleotide position 25, causing the alanine (A) at amino acid position 9 to be replaced by a proline (P). 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

0.27

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.75

M_CAP

Benign

0.0076

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.88

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.010

REVEL

Benign

0.18

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.0020

Vest4

0.37

MutPred

0.26

Loss of helix (P = 0.0033);

MVP

0.65

MPC

0.84

ClinPred

0.89

GERP RS

5.0

Varity_R

0.32

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over