12-53297875-A-G

Variant names:

• chr12-53297875-A-G
• NM_002624.4:c.233A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002624.4(PFDN5):​c.233A>G​(p.Asp78Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PFDN5 NM_002624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

Genes affected

PFDN5 (HGNC:8869): (prefoldin subunit 5) This gene encodes a member of the prefoldin alpha 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. The encoded protein may also repress the transcriptional activity of the proto-oncogene c-Myc. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ENSG00000288663 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN5	NM_002624.4	c.233A>G	p.Asp78Gly	missense_variant	Exon 4 of 6	ENST00000334478.9	NP_002615.2
PFDN5	NM_145897.3	c.98A>G	p.Asp33Gly	missense_variant	Exon 2 of 4		NP_665904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN5	ENST00000334478.9	c.233A>G	p.Asp78Gly	missense_variant	Exon 4 of 6	1	NM_002624.4	ENSP00000334188.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.233A>G (p.D78G) alteration is located in exon 4 (coding exon 4) of the PFDN5 gene. This alteration results from a A to G substitution at nucleotide position 233, causing the aspartic acid (D) at amino acid position 78 to be replaced by a glycine (G). 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	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Uncertain	0.42	T;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Pathogenic	0.78
Sift	Benign	0.034	D;D;D
Sift4G	Uncertain	0.058	T;D;T
Polyphen		0.058	B;.;B
Vest4		0.70
MutPred		0.68		Loss of sheet (P = 0.0126);.;Loss of sheet (P = 0.0126);
MVP		0.87
MPC		0.32
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.73
gMVP		0.71

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: chr12-53691659;