rs464865

chr6-33289409-A-G

Variant summary

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

The ENST00000395131.5(PFDN6):c.-299A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,307,812 control chromosomes in the GnomAD database, including 191,645 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 0.59 (27410 hom., cov: 32)
  • Exomes 𝑓: 0.53 (164235 hom.)
• Consequence: PFDN6 ENST00000395131.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

Genes affected

PFDN6 (HGNC:4926): (prefoldin subunit 6) PFDN6 is a subunit of the heteromeric prefoldin complex that chaperones nascent actin (see MIM 102560) and alpha- and beta-tubulin (see MIM 602529 and MIM 191130, respectively) chains pending their transfer to the cytosolic chaperonin containing TCP1 (MIM 186980) (CCT) complex (Hansen et al., 1999 [PubMed 10209023]).[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFDN6	XM_047418077.1	c.-88+129A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFDN6	ENST00000395131.5	c.-299A>G		5_prime_UTR_variant	1/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89976 AN: 151942 Hom.: 27357 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.530 AC: 612684 AN: 1155752 Hom.: 164235 Cov.: 38 AF XY: 0.531 AC XY: 292820 AN XY: 550978

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.622

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.592 AC: 90082 AN: 152060 Hom.: 27410 Cov.: 32 AF XY: 0.592 AC XY: 44038 AN XY: 74342

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.587

Alfa AF: 0.552 Hom.: 13494

Bravo AF: 0.601

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.2
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs464865; hg19: chr6-33257186;