12-53297857-T-C

Variant names:

• chr12-53297857-T-C
• rs1944172870
• NM_002624.4:c.215T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002624.4(PFDN5):​c.215T>C​(p.Val72Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V72D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PFDN5 NM_002624.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN5	NM_002624.4	MANE Select	c.215T>C	p.Val72Ala	missense	Exon 4 of 6	NP_002615.2
	PFDN5	NM_145897.3		c.80T>C	p.Val27Ala	missense	Exon 2 of 4	NP_665904.1	Q99471-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN5	ENST00000334478.9	TSL:1 MANE Select	c.215T>C	p.Val72Ala	missense	Exon 4 of 6	ENSP00000334188.4	Q99471-1
	PFDN5	ENST00000551018.5	TSL:1	c.215T>C	p.Val72Ala	missense	Exon 4 of 6	ENSP00000447942.1	Q99471-1
	PFDN5	ENST00000351500.7	TSL:1	c.80T>C	p.Val27Ala	missense	Exon 2 of 4	ENSP00000266964.4	Q99471-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.92
MutPred		0.83		Gain of disorder (P = 0.0447)
MVP		0.76
MPC		0.70
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.79
gMVP		0.73
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1944172870; hg19: chr12-53691641;