6-33289409-A-G

Variant names:

• chr6-33289409-A-G
• rs464865
• ENST00000395131.5:c.-299A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

WDR46 (HGNC:13923): (WD repeat domain 46) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395131.5. 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
	WDR46	NM_005452.6	MANE Select	c.-239T>C		upstream_gene	N/A	NP_005443.3
	PFDN6	NM_001185181.3	MANE Select	c.-448A>G		upstream_gene	N/A	NP_001172110.1	O15212
	WDR46	NM_001164267.2		c.-239T>C		upstream_gene	N/A	NP_001157739.1	A0A1U9X8W1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN6	ENST00000395131.5	TSL:1	c.-299A>G		5_prime_UTR	Exon 1 of 5	ENSP00000378563.1	O15212
	PFDN6	ENST00000883725.1		c.-88+129A>G		intron	N/A	ENSP00000553784.1
	PFDN6	ENST00000940443.1		c.-88+129A>G		intron	N/A	ENSP00000610502.1

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

African (AFR) AF: 0.749 AC: 18317 AN: 24466

American (AMR) AF: 0.549 AC: 6657 AN: 12128

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 9474 AN: 15854

East Asian (EAS) AF: 0.344 AC: 10213 AN: 29678

South Asian (SAS) AF: 0.622 AC: 21883 AN: 35168

European-Finnish (FIN) AF: 0.529 AC: 13316 AN: 25178

Middle Eastern (MID) AF: 0.570 AC: 1797 AN: 3154

European-Non Finnish (NFE) AF: 0.524 AC: 504777 AN: 962732

Other (OTH) AF: 0.554 AC: 26250 AN: 47394

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

African (AFR) AF: 0.737 AC: 30541 AN: 41456

American (AMR) AF: 0.579 AC: 8843 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3472

East Asian (EAS) AF: 0.390 AC: 2018 AN: 5172

South Asian (SAS) AF: 0.623 AC: 3007 AN: 4824

European-Finnish (FIN) AF: 0.527 AC: 5560 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36251 AN: 67998

Other (OTH) AF: 0.587 AC: 1236 AN: 2104

Alfa AF: 0.579 Hom.: 32117

Bravo AF: 0.601

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		-0.81
PromoterAI		-0.017	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs464865; hg19: chr6-33257186;