chr12-53299320-C-T

Variant names:

• chr12-53299320-C-T
• rs766994081
• NM_002624.4:c.440C>T

Variant summary

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

The NM_002624.4(PFDN5):​c.440C>T​(p.Ala147Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,572 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PFDN5 NM_002624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27
• Publications: 1 publications found

Genes affected

PFDN5 (HGNC:8869): (prefoldin subunit 5) This gene encodes a member of the prefoldin alpha 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. The encoded protein may also repress the transcriptional activity of the proto-oncogene c-Myc. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ENSG00000288663 (HGNC:):

MYG1-AS1 (HGNC:54810): (MYG1 antisense RNA 1)

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=0.17739382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002624.4. 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
	PFDN5	NM_002624.4	MANE Select	c.440C>T	p.Ala147Val	missense	Exon 6 of 6	NP_002615.2
	PFDN5	NM_145897.3		c.305C>T	p.Ala102Val	missense	Exon 4 of 4	NP_665904.1	Q99471-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFDN5	ENST00000334478.9	TSL:1 MANE Select	c.440C>T	p.Ala147Val	missense	Exon 6 of 6	ENSP00000334188.4	Q99471-1
	PFDN5	ENST00000551018.5	TSL:1	c.440C>T	p.Ala147Val	missense	Exon 6 of 6	ENSP00000447942.1	Q99471-1
	PFDN5	ENST00000351500.7	TSL:1	c.305C>T	p.Ala102Val	missense	Exon 4 of 4	ENSP00000266964.4	Q99471-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250914 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459426 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726144

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52640

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110600

Other (OTH) AF: 0.0000166 AC: 1 AN: 60316

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.15
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.083
Sift	Uncertain	0.021	D
Sift4G	Benign	0.088	T
Polyphen		0.75	P
Vest4		0.22
MutPred		0.29		Gain of loop (P = 0.0051)
MVP		0.49
MPC		0.17
ClinPred		0.79	D
GERP RS		4.2
PromoterAI		-0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.38
Mutation Taster		=74/26	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: rs766994081; hg19: chr12-53693104;