rs2694861

Positions:

• chr12-53298178-C-A
• chr12-53298178-C-G
• chr12-53298178-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002624.4(PFDN5):​c.388+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,395,070 control chromosomes in the GnomAD database, including 656,226 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (64470 hom., cov: 33)
  • Exomes 𝑓: 0.97 (591756 hom.)
• Consequence: PFDN5 NM_002624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFDN5	NM_002624.4	c.388+28C>A		intron_variant		ENST00000334478.9
PFDN5	NM_145897.3	c.253+28C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFDN5	ENST00000334478.9	c.388+28C>A		intron_variant		1	NM_002624.4	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139019 AN: 152142 Hom.: 64439 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.915

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.946

GnomAD3 exomes AF: 0.961 AC: 239920 AN: 249682 Hom.: 115791 AF XY: 0.963 AC XY: 130039 AN XY: 135094

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.982

Gnomad ASJ exome AF: 0.990

Gnomad EAS exome AF: 0.960

Gnomad SAS exome AF: 0.926

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.975 AC: 1211593 AN: 1242810 Hom.: 591756 Cov.: 17 AF XY: 0.974 AC XY: 613077 AN XY: 629318

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.979

Gnomad4 ASJ exome AF: 0.990

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.986

Gnomad4 OTH exome AF: 0.961

GnomAD4 genome AF: 0.914 AC: 139104 AN: 152260 Hom.: 64470 Cov.: 33 AF XY: 0.915 AC XY: 68147 AN XY: 74472

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.946

Alfa AF: 0.962 Hom.: 22131

Bravo AF: 0.904

Asia WGS AF: 0.918 AC: 3194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs2694861; hg19: chr12-53691962;