20-54219074-G-C

Variant names:

• chr20-54219074-G-C
• NM_002623.4:c.329G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002623.4(PFDN4):​c.329G>C​(p.Arg110Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,437,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R110Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PFDN4 NM_002623.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44

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]

ACMG classification

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=0.24139833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN4	NM_002623.4	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 4	ENST00000371419.7	NP_002614.2
PFDN4	XM_047440198.1	c.575G>C	p.Arg192Pro	missense_variant	Exon 4 of 4		XP_047296154.1
PFDN4	XM_017027879.2	c.470G>C	p.Arg157Pro	missense_variant	Exon 4 of 4		XP_016883368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN4	ENST00000371419.7	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 4	1	NM_002623.4	ENSP00000360473.2
PFDN4	ENST00000441080.2	n.329G>C		non_coding_transcript_exon_variant	Exon 4 of 6	5		ENSP00000432441.1
PFDN4	ENST00000487129.1	n.633G>C		non_coding_transcript_exon_variant	Exon 5 of 5	2
PFDN4	ENST00000493356.5	n.448G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437068 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 714778

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.065
Sift	Benign	0.27	T
Sift4G	Benign	0.26	T
Polyphen		0.47	P
Vest4		0.41
MutPred		0.47		Loss of MoRF binding (P = 0.0053);
MVP		0.48
MPC		1.3
ClinPred		0.74	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-52835613;