chr6-33289409-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000395131.5(PFDN6):​c.-299A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000865 in 1,156,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: PFDN6 ENST00000395131.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>A		upstream_gene	N/A	NP_005443.3
	PFDN6	NM_001185181.3	MANE Select	c.-448A>T		upstream_gene	N/A	NP_001172110.1	O15212
	WDR46	NM_001164267.2		c.-239T>A		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>T		5_prime_UTR	Exon 1 of 5	ENSP00000378563.1	O15212
	PFDN6	ENST00000883725.1		c.-88+129A>T		intron	N/A	ENSP00000553784.1
	PFDN6	ENST00000940443.1		c.-88+129A>T		intron	N/A	ENSP00000610502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.65e-7 AC: 1 AN: 1156408 Hom.: 0 Cov.: 38 AF XY: 0.00000181 AC XY: 1 AN XY: 551324

African (AFR) AF: 0.00 AC: 0 AN: 24474

American (AMR) AF: 0.00 AC: 0 AN: 12146

Ashkenazi Jewish (ASJ) AF: 0.0000631 AC: 1 AN: 15860

East Asian (EAS) AF: 0.00 AC: 0 AN: 29698

South Asian (SAS) AF: 0.00 AC: 0 AN: 35248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 963172

Other (OTH) AF: 0.00 AC: 0 AN: 47440

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		-0.81
PromoterAI		0.014	Neutral

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: rs464865; hg19: chr6-33257186;