6-33290842-C-A

Variant names:

• chr6-33290842-C-A
• rs743946
• NM_001185181.3:c.387C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001185181.3(PFDN6):​c.387C>A​(p.Ala129Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,597,544 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (134 hom.)
• Consequence: PFDN6 NM_001185181.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 6-33290842-C-A is Benign according to our data. Variant chr6-33290842-C-A is described in ClinVar as Benign. ClinVar VariationId is 776124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185181.3. 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
	PFDN6	NM_001185181.3	MANE Select	c.387C>A	p.Ala129Ala	synonymous	Exon 4 of 4	NP_001172110.1	O15212
	PFDN6	NM_001265595.2		c.387C>A	p.Ala129Ala	synonymous	Exon 5 of 5	NP_001252524.1	Q5STK2
	PFDN6	NM_001265596.1		c.387C>A	p.Ala129Ala	synonymous	Exon 5 of 5	NP_001252525.1	O15212

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN6	ENST00000374606.10	TSL:1 MANE Select	c.387C>A	p.Ala129Ala	synonymous	Exon 4 of 4	ENSP00000363734.5	O15212
	PFDN6	ENST00000395131.5	TSL:1	c.387C>A	p.Ala129Ala	synonymous	Exon 5 of 5	ENSP00000378563.1	O15212
	PFDN6	ENST00000374607.5	TSL:2	c.387C>A	p.Ala129Ala	synonymous	Exon 5 of 5	ENSP00000363735.1	O15212

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3556 AN: 151896 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0221

GnomAD2 exomes AF: 0.00654 AC: 1503 AN: 229862 AF XY: 0.00487

Gnomad AFR exome AF: 0.0820

Gnomad AMR exome AF: 0.00710

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000810

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00285 AC: 4125 AN: 1445530 Hom.: 134 Cov.: 34 AF XY: 0.00252 AC XY: 1814 AN XY: 719408

African (AFR) AF: 0.0805 AC: 2685 AN: 33362

American (AMR) AF: 0.00780 AC: 346 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.000478 AC: 41 AN: 85862

European-Finnish (FIN) AF: 0.0000741 AC: 3 AN: 40492

Middle Eastern (MID) AF: 0.0115 AC: 66 AN: 5720

European-Non Finnish (NFE) AF: 0.000507 AC: 563 AN: 1109930

Other (OTH) AF: 0.00700 AC: 421 AN: 60144

GnomAD4 genome AF: 0.0237 AC: 3600 AN: 152014 Hom.: 143 Cov.: 32 AF XY: 0.0239 AC XY: 1778 AN XY: 74318

African (AFR) AF: 0.0805 AC: 3335 AN: 41430

American (AMR) AF: 0.0112 AC: 171 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000589 AC: 40 AN: 67966

Other (OTH) AF: 0.0218 AC: 46 AN: 2108

Alfa AF: 0.0141 Hom.: 12

Bravo AF: 0.0268

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743946; hg19: chr6-33258619;