Genetic Variant NM_002622.5:c.308G>A (chr5-140246035-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002622.5(PFDN1):c.308G>A(p.Arg103Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000256 in 1,561,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PFDN1
NM_002622.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Publications

0 publications found

Variant links:

Genes affected

PFDN1 (HGNC:8866): (prefoldin subunit 1) This gene encodes a member of the prefoldin beta 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. [provided by RefSeq, Jul 2008]

PFDN1 links:

CYSTM1 (HGNC:30239): (cysteine rich transmembrane module containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CYSTM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29589942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002622.5. 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
	PFDN1	NM_002622.5	MANE Select	c.308G>A	p.Arg103Gln	missense	Exon 4 of 4	NP_002613.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFDN1	ENST00000261813.9	TSL:1 MANE Select	c.308G>A	p.Arg103Gln	missense	Exon 4 of 4	ENSP00000261813.4	O60925
PFDN1	ENST00000893784.1		c.305G>A	p.Arg102Gln	missense	Exon 4 of 4	ENSP00000563843.1
PFDN1	ENST00000934220.1		c.56G>A	p.Arg19Gln	missense	Exon 2 of 2	ENSP00000604279.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000408

AC:

AN:

171416

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000765

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.000425

GnomAD4 exome

AF:

0.0000234

AC:

AN:

1408862

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

695932

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32308

American (AMR)

AF:

0.0000539

AC:

AN:

37072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25336

East Asian (EAS)

AF:

0.00

AC:

AN:

37114

South Asian (SAS)

AF:

0.0000125

AC:

AN:

79996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000277

AC:

AN:

1082960

Other (OTH)

AF:

0.00

AC:

AN:

58392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000171

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.036

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

PhyloP100

6.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.0

REVEL

Benign

0.10

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

0.51

Vest4

0.57

MVP

0.37

MPC

0.46

ClinPred

0.099

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.47

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over