Genetic Variant ENO3:c.-3+191_-3+192delCC (chr17-4948563-TCC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000572383.1(PFN1):c.77-10_77-9delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 462,512 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

PFN1
ENST00000572383.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

ENO3 (HGNC:3354): (enolase 3) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme is found in skeletal muscle cells in the adult where it may play a role in muscle development and regeneration. A switch from alpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene have be associated glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jul 2010]

ENO3 links:

PFN1 (HGNC:8881): (profilin 1) This gene encodes a member of the profilin family of small actin-binding proteins. The encoded protein plays an important role in actin dynamics by regulating actin polymerization in response to extracellular signals. Deletion of this gene is associated with Miller-Dieker syndrome, and the encoded protein may also play a role in Huntington disease. Multiple pseudogenes of this gene are located on chromosome 1. [provided by RefSeq, Jul 2012]

PFN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PFN1	NM_005022.4 link	c.-171_-170delGG	upstream_gene_variant	ENST00000225655.6	NP_005013.1	P07737
PFN1	NM_001375991.1 link	c.-171_-170delGG	upstream_gene_variant		NP_001362920.1
ENO3	XM_011523729.2 link	c.-732_-731delCC	upstream_gene_variant		XP_011522031.1	P13929-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENO3	ENST00000520221.5 link	c.-3+191_-3+192delCC	intron_variant	Intron 1 of 6	5		ENSP00000467444.1	K7EPM1
PFN1	ENST00000572383.1 link	c.77-10_77-9delGG	intron_variant	Intron 1 of 2	3		ENSP00000460363.1	I3L3D5
ENO3	ENST00000519266.5 link	c.-3+217_-3+218delCC	intron_variant	Intron 1 of 1	3		ENSP00000467270.1	K7EP84
PFN1	ENST00000225655.6 link	c.-171_-170delGG	upstream_gene_variant		1	NM_005022.4	ENSP00000225655.5	P07737

Frequencies

GnomAD3 genomes

AF:

0.0000163

AC:

AN:

122416

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000817

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:

0.00

GnomAD3 exomes

AF:

0.00215

AC:

AN:

932

Hom.:

AF XY:

0.00185

AC XY:

AN XY:

540

show subpopulations

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:

0.00300

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000297

AC:

101

AN:

340096

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

174980

show subpopulations

Gnomad4 AFR exome

AF:

0.000146

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000112

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.000227

Gnomad4 FIN exome

AF:

0.0000458

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.000325

GnomAD4 genome

AF:

0.0000163

AC:

AN:

122416

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

59194

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.0000817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over