Genetic Variant PFDN6:p.Ala129Ala (chr6-33290842-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.45

Variant links:

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]

PFDN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN6	NM_001185181.3 link	c.387C>A	p.Ala129Ala	synonymous_variant	Exon 4 of 4	ENST00000374606.10	NP_001172110.1	O15212Q5STK2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN6	ENST00000374606.10 link	c.387C>A	p.Ala129Ala	synonymous_variant	Exon 4 of 4	1	NM_001185181.3	ENSP00000363734.5		O15212

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3556

AN:

151896

Hom.:

135

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00654

AC:

1503

AN:

229862

Hom.:

AF XY:

0.00487

AC XY:

615

AN XY:

126298

show subpopulations

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 SAS exome

AF:

0.000535

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.:

AF XY:

0.00252

AC XY:

1814

AN XY:

719408

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.00780

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000478

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.000507

Gnomad4 OTH exome

AF:

0.00700

GnomAD4 genome

AF:

0.0237

AC:

3600

AN:

152014

Hom.:

143

Cov.:

AF XY:

0.0239

AC XY:

1778

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000589

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.0268

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over