Variant 20-54219074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002623.4(PFDN4):c.329G>A(p.Arg110Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000887 in 1,589,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

PFDN4
NM_002623.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.007881254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFDN4	NM_002623.4 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	4/4	ENST00000371419.7	NP_002614.2	Q9NQP4
PFDN4	XM_047440198.1 linkuse as main transcript	c.575G>A	p.Arg192Gln	missense_variant	4/4		XP_047296154.1
PFDN4	XM_017027879.2 linkuse as main transcript	c.470G>A	p.Arg157Gln	missense_variant	4/4		XP_016883368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PFDN4	ENST00000371419.7 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	4/4	1	NM_002623.4	ENSP00000360473.2	Q9NQP4
PFDN4	ENST00000441080.2 linkuse as main transcript	n.329G>A		non_coding_transcript_exon_variant	4/6	5		ENSP00000432441.1	E9PQY2
PFDN4	ENST00000487129.1 linkuse as main transcript	n.633G>A		non_coding_transcript_exon_variant	5/5	2
PFDN4	ENST00000493356.5 linkuse as main transcript	n.448G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000112

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:

0.00376

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000161

AC:

AN:

236078

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

127954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

AF:

0.0000863

AC:

124

AN:

1437070

Hom.:

Cov.:

AF XY:

0.0000937

AC XY:

AN XY:

714780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00338

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000264

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.000112

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00376

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.000124

AC:

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

Aug 08, 2023

The c.329G>A (p.R110Q) alteration is located in exon 4 (coding exon 4) of the PFDN4 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a glutamine (Q). 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

0.055

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.053

Eigen

Benign

-0.31

Eigen_PC

Benign

0.0035

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

PrimateAI

Benign

0.38

PROVEAN

Benign

0.94

REVEL

Benign

0.051

Sift

Benign

0.60

Sift4G

Benign

0.62

Polyphen

0.0040

Vest4

0.11

MVP

0.31

MPC

0.74

ClinPred

0.064

GERP RS

5.6

Varity_R

0.21

gMVP

0.094

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