chr5-140300497-G-T

Variant names:

• chr5-140300497-G-T
• NM_002622.5:c.119C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002622.5(PFDN1):​c.119C>A​(p.Thr40Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PFDN1 NM_002622.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25346434).

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.119C>A	p.Thr40Lys	missense	Exon 2 of 4	NP_002613.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN1	ENST00000261813.9	TSL:1 MANE Select	c.119C>A	p.Thr40Lys	missense	Exon 2 of 4	ENSP00000261813.4	O60925
	PFDN1	ENST00000893784.1		c.119C>A	p.Thr40Lys	missense	Exon 2 of 4	ENSP00000563843.1
	PFDN1	ENST00000524074.1	TSL:5	c.119C>A	p.Thr40Lys	missense	Exon 2 of 5	ENSP00000428707.1	E5RGS4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459478 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 726216

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109944

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.085
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.43	T
Sift4G	Benign	0.92	T
Polyphen		0.38	B
Vest4		0.50
MutPred		0.32		Loss of stability (P = 0.0066)
MVP		0.36
MPC		0.47
ClinPred		0.87	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.47
Mutation Taster		=69/31	polymorphism

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

hg19: chr5-139680082;