NM_002622.5:c.226A>G

Variant names:

• chr5-140281508-T-C
• rs1302660731
• NM_002622.5:c.226A>G

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.226A>G​(p.Ile76Val) variant causes a missense change. 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)
• Consequence: PFDN1 NM_002622.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83
• 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]

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

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=0.23650208).

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.226A>G	p.Ile76Val	missense	Exon 3 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.226A>G	p.Ile76Val	missense	Exon 3 of 4	ENSP00000261813.4	O60925
	PFDN1	ENST00000893784.1		c.226A>G	p.Ile76Val	missense	Exon 3 of 4	ENSP00000563843.1
	PFDN1	ENST00000524074.1	TSL:5	c.226A>G	p.Ile76Val	missense	Exon 3 of 5	ENSP00000428707.1	E5RGS4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.075
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.12
Sift	Benign	0.40	T
Sift4G	Benign	0.67	T
Polyphen		0.64	P
Vest4		0.32
MutPred		0.46		Loss of catalytic residue at L81 (P = 0.027)
MVP		0.39
MPC		0.41
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.26
Mutation Taster		=87/13	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

dbSNP: rs1302660731; hg19: chr5-139661093;