rs376068871

Variant names:

• chr17-4948563-TCCC-T
• rs376068871
• ENST00000896245.1:c.-3+200_-3+202delCCC

Your query was ambiguous. Multiple possible variants found:

• chr17-4948563-TCCC-T
• chr17-4948563-TCCC-TC
• chr17-4948563-TCCC-TCC
• chr17-4948563-TCCC-TCCCC
• chr17-4948563-TCCC-TCCCCC
• chr17-4948563-TCCC-TCCCCCC
• chr17-4948563-TCCC-TCCCCCCC
• chr17-4948563-TCCC-TCCCCCCCC
• chr17-4948563-TCCC-TCCCCCCCCC
• chr17-4948563-TCCC-TCCCCCCCCCCC
• chr17-4948563-TCCC-TCCCCCCCCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

PFN1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572383.1. 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
	PFN1	NM_005022.4	MANE Select	c.-172_-170delGGG		upstream_gene	N/A	NP_005013.1	P07737
	PFN1	NM_001375991.1		c.-172_-170delGGG		upstream_gene	N/A	NP_001362920.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO3	ENST00000896245.1		c.-3+200_-3+202delCCC		intron	N/A	ENSP00000566304.1
	ENO3	ENST00000520221.5	TSL:5	c.-3+191_-3+193delCCC		intron	N/A	ENSP00000467444.1	K7EPM1
	PFN1	ENST00000572383.1	TSL:3	c.77-11_77-9delGGG		intron	N/A	ENSP00000460363.1	I3L3D5

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

African (AFR) AF: 0.00 AC: 0 AN: 6878

American (AMR) AF: 0.00 AC: 0 AN: 6380

Ashkenazi Jewish (ASJ) AF: 0.000112 AC: 1 AN: 8938

East Asian (EAS) AF: 0.00 AC: 0 AN: 19394

South Asian (SAS) AF: 0.00 AC: 0 AN: 22078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1432

European-Non Finnish (NFE) AF: 0.00000424 AC: 1 AN: 235614

Other (OTH) AF: 0.00 AC: 0 AN: 18510

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=296/4	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: rs376068871; hg19: chr17-4851858;