chr20-54219043-G-T

Variant names:

• chr20-54219043-G-T
• rs368220174
• NM_002623.4:c.298G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002623.4(PFDN4):​c.298G>T​(p.Ala100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A100T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PFDN4 NM_002623.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06323394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN4	NM_002623.4	c.298G>T	p.Ala100Ser	missense_variant	Exon 4 of 4	ENST00000371419.7	NP_002614.2
PFDN4	XM_047440198.1	c.544G>T	p.Ala182Ser	missense_variant	Exon 4 of 4		XP_047296154.1
PFDN4	XM_017027879.2	c.439G>T	p.Ala147Ser	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.298G>T	p.Ala100Ser	missense_variant	Exon 4 of 4	1	NM_002623.4	ENSP00000360473.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.65	N
PhyloP100		3.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.043
Sift	Benign	0.63	T
Sift4G	Benign	0.80	T
Polyphen		0.049	B
Vest4		0.083
MutPred		0.40		Gain of disorder (P = 0.0375);
MVP		0.22
MPC		0.61
ClinPred		0.57	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.087
Mutation Taster		=94/6	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: rs368220174; hg19: chr20-52835582;