chr17-4948563-TCCC-T

Variant names:

• chr17-4948563-TCCC-T
• ENST00000520221.5:c.-3+191_-3+193delCCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000572383.1(PFN1):​c.77-11_77-9delGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 341,136 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: not found (cov: 28)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: PFN1 ENST00000572383.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFN1	NM_005022.4	c.-172_-170delGGG		upstream_gene_variant		ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1	c.-172_-170delGGG		upstream_gene_variant			NP_001362920.1
ENO3	XM_011523729.2	c.-732_-730delCCC		upstream_gene_variant			XP_011522031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO3	ENST00000520221.5	c.-3+191_-3+193delCCC		intron_variant	Intron 1 of 6	5		ENSP00000467444.1
PFN1	ENST00000572383.1	c.77-11_77-9delGGG		intron_variant	Intron 1 of 2	3		ENSP00000460363.1
ENO3	ENST00000519266.5	c.-3+217_-3+219delCCC		intron_variant	Intron 1 of 1	3		ENSP00000467270.1
PFN1	ENST00000225655.6	c.-172_-170delGGG		upstream_gene_variant		1	NM_005022.4	ENSP00000225655.5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000586 AC: 2 AN: 341136 Hom.: 0 AF XY: 0.00000570 AC XY: 1 AN XY: 175536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000424

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4851858;