NM_001185181.3:c.379G>T

Variant names:

• chr6-33290834-G-T
• rs767083338
• NM_001185181.3:c.379G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001185181.3(PFDN6):​c.379G>T​(p.Gly127Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,046 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: 6.9e-7 (0 hom.)
• Consequence: PFDN6 NM_001185181.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29562116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFDN6	NM_001185181.3	c.379G>T	p.Gly127Cys	missense_variant	Exon 4 of 4	ENST00000374606.10	NP_001172110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFDN6	ENST00000374606.10	c.379G>T	p.Gly127Cys	missense_variant	Exon 4 of 4	1	NM_001185181.3	ENSP00000363734.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233656 Hom.: 0 AF XY: 0.00000781 AC XY: 1 AN XY: 128106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000923

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1448046 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 720682

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T;T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.37	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.26
MutPred		0.26		Gain of catalytic residue at P126 (P = 0.0161);Gain of catalytic residue at P126 (P = 0.0161);Gain of catalytic residue at P126 (P = 0.0161);Gain of catalytic residue at P126 (P = 0.0161);
MVP		0.46
MPC		0.85
ClinPred		0.50	T
GERP RS		5.5
Varity_R		0.30
gMVP		0.57

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

Other links and lift over

dbSNP: rs767083338; hg19: chr6-33258611;