rs2694861

Variant names:

• chr12-53298178-C-A
• rs2694861
• NM_002624.4:c.388+28C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-53298178-C-A
• chr12-53298178-C-G
• chr12-53298178-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002624.4(PFDN5):​c.388+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,395,070 control chromosomes in the GnomAD database, including 656,226 homozygotes. 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: 𝑓 0.91 (64470 hom., cov: 33)
  • Exomes 𝑓: 0.97 (591756 hom.)
• Consequence: PFDN5 NM_002624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 9 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

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.388+28C>A		intron	N/A	NP_002615.2
	PFDN5	NM_145897.3		c.253+28C>A		intron	N/A	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.388+28C>A		intron	N/A	ENSP00000334188.4	Q99471-1
	PFDN5	ENST00000551018.5	TSL:1	c.388+28C>A		intron	N/A	ENSP00000447942.1	Q99471-1
	PFDN5	ENST00000351500.7	TSL:1	c.253+28C>A		intron	N/A	ENSP00000266964.4	Q99471-3

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139019 AN: 152142 Hom.: 64439 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.915

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.946

GnomAD2 exomes AF: 0.961 AC: 239920 AN: 249682 AF XY: 0.963

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.982

Gnomad ASJ exome AF: 0.990

Gnomad EAS exome AF: 0.960

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.975 AC: 1211593 AN: 1242810 Hom.: 591756 Cov.: 17 AF XY: 0.974 AC XY: 613077 AN XY: 629318

African (AFR) AF: 0.731 AC: 21294 AN: 29126

American (AMR) AF: 0.979 AC: 43525 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 24534 AN: 24776

East Asian (EAS) AF: 0.978 AC: 37865 AN: 38724

South Asian (SAS) AF: 0.928 AC: 75894 AN: 81786

European-Finnish (FIN) AF: 0.998 AC: 53107 AN: 53218

Middle Eastern (MID) AF: 0.955 AC: 5075 AN: 5312

European-Non Finnish (NFE) AF: 0.986 AC: 899273 AN: 912326

Other (OTH) AF: 0.961 AC: 51026 AN: 53076

GnomAD4 genome AF: 0.914 AC: 139104 AN: 152260 Hom.: 64470 Cov.: 33 AF XY: 0.915 AC XY: 68147 AN XY: 74472

African (AFR) AF: 0.740 AC: 30718 AN: 41506

American (AMR) AF: 0.964 AC: 14750 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3441 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4959 AN: 5176

South Asian (SAS) AF: 0.916 AC: 4427 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10621 AN: 10624

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67008 AN: 68040

Other (OTH) AF: 0.946 AC: 1997 AN: 2110

Alfa AF: 0.969 Hom.: 36517

Bravo AF: 0.904

Asia WGS AF: 0.918 AC: 3194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs2694861; hg19: chr12-53691962;