Variant 17-4948563-TC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000572383.1(PFN1):c.77-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 421,292 control chromosomes in the GnomAD database, including 2,629 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 730 hom., cov: 28)

Exomes 𝑓: 0.18 ( 1899 hom. )

Consequence

PFN1
ENST00000572383.1 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 17-4948563-TC-T is Benign according to our data. Variant chr17-4948563-TC-T is described in ClinVar as [Benign]. Clinvar id is 1228307.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFN1	NM_005022.4 linkuse as main transcript			upstream_gene_variant		ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1 linkuse as main transcript			upstream_gene_variant			NP_001362920.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ENO3	ENST00000519266.5 linkuse as main transcript	c.-3+226del	intron_variant	3		ENSP00000467270
ENO3	ENST00000520221.5 linkuse as main transcript	c.-3+200del	intron_variant	5		ENSP00000467444
PFN1	ENST00000572383.1 linkuse as main transcript	c.77-9del	splice_polypyrimidine_tract_variant, intron_variant	3		ENSP00000460363
PFN1	ENST00000225655.6 linkuse as main transcript		upstream_gene_variant	1	NM_005022.4	ENSP00000225655	P1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

12886

AN:

122284

Hom.:

729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0397

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0536

Gnomad SAS

AF:

0.0504

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.0919

GnomAD3 exomes

AF:

0.376

AC:

350

AN:

932

Hom.:

AF XY:

0.378

AC XY:

204

AN XY:

540

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.185

AC:

55234

AN:

298980

Hom.:

1899

Cov.:

AF XY:

0.184

AC XY:

28271

AN XY:

153298

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.0934

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.105

AC:

12888

AN:

122312

Hom.:

730

Cov.:

AF XY:

0.107

AC XY:

6340

AN XY:

59184

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.0778

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.0538

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.0915

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over