17-4948563-TCCC-TCCCCC

Variant names:

• chr17-4948563-T-TCC
• rs376068871
• ENST00000520221.5:c.-3+190_-3+191insCC

Variant summary

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

The ENST00000572383.1(PFN1):​c.77-9_77-8insGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 463,476 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 0.00038 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00057 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFN1	NM_005022.4	c.-170_-169insGG		upstream_gene_variant		ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1	c.-170_-169insGG		upstream_gene_variant			NP_001362920.1
ENO3	XM_011523729.2	c.-733_-732insCC		upstream_gene_variant			XP_011522031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO3	ENST00000520221.5	c.-3+190_-3+191insCC		intron_variant	Intron 1 of 6	5		ENSP00000467444.1
PFN1	ENST00000572383.1	c.77-9_77-8insGG		intron_variant	Intron 1 of 2	3		ENSP00000460363.1
ENO3	ENST00000519266.5	c.-3+216_-3+217insCC		intron_variant	Intron 1 of 1	3		ENSP00000467270.1
PFN1	ENST00000225655.6	c.-170_-169insGG		upstream_gene_variant		1	NM_005022.4	ENSP00000225655.5

Frequencies

GnomAD3 genomes AF: 0.000384 AC: 47 AN: 122418 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00303

Gnomad EAS AF: 0.000478

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00394

Gnomad NFE AF: 0.000380

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000572 AC: 195 AN: 341028 Hom.: 0 Cov.: 3 AF XY: 0.000570 AC XY: 100 AN XY: 175468

Gnomad4 AFR exome AF: 0.000873

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00403

Gnomad4 EAS exome AF: 0.00165

Gnomad4 SAS exome AF: 0.000408

Gnomad4 FIN exome AF: 0.0000913

Gnomad4 NFE exome AF: 0.000348

Gnomad4 OTH exome AF: 0.000811

GnomAD4 genome AF: 0.000384 AC: 47 AN: 122448 Hom.: 0 Cov.: 28 AF XY: 0.000473 AC XY: 28 AN XY: 59242

Gnomad4 AFR AF: 0.000161

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00303

Gnomad4 EAS AF: 0.000480

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000380

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376068871; hg19: chr17-4851858;