20-54214367-A-T

Variant names:

• chr20-54214367-A-T
• rs772902032
• NM_002623.4:c.41A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002623.4(PFDN4):​c.41A>T​(p.Asn14Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,433,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N14S) 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: 6.78
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN4	NM_002623.4	c.41A>T	p.Asn14Ile	missense_variant	Exon 2 of 4	ENST00000371419.7	NP_002614.2
PFDN4	XM_047440198.1	c.287A>T	p.Asn96Ile	missense_variant	Exon 2 of 4		XP_047296154.1
PFDN4	XM_017027879.2	c.182A>T	p.Asn61Ile	missense_variant	Exon 2 of 4		XP_016883368.1
PFDN4	XM_047440199.1	c.287A>T	p.Asn96Ile	missense_variant	Exon 2 of 3		XP_047296155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN4	ENST00000371419.7	c.41A>T	p.Asn14Ile	missense_variant	Exon 2 of 4	1	NM_002623.4	ENSP00000360473.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433748 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 714540

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.00 AC: 0 AN: 43386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 84128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091568

Other (OTH) AF: 0.00 AC: 0 AN: 59318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.21
Sift	Benign	0.030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.55	P
Vest4		0.68
MutPred		0.45		Loss of disorder (P = 0.0265);
MVP		0.73
MPC		0.97
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.36
gMVP		0.67
Mutation Taster		=72/28	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: rs772902032; hg19: chr20-52830906;