Genetic Variant ENST00000520221.5:c.-3+190_-3+191insC (chr17-4948563-T-TC) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The ENST00000520221.5(ENO3):c.-3+190_-3+191insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 458,360 control chromosomes in the GnomAD database, including 383 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.064 ( 323 hom., cov: 28)

Exomes 𝑓: 0.076 ( 60 hom. )

Consequence

ENO3
ENST00000520221.5 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-T-TC is Benign according to our data. Variant chr17-4948563-T-TC is described in ClinVar as [Benign]. Clinvar id is 1295407.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PFN1	NM_005022.4 link	c.-170_-169insG	upstream_gene_variant	ENST00000225655.6	NP_005013.1	P07737
PFN1	NM_001375991.1 link	c.-170_-169insG	upstream_gene_variant		NP_001362920.1
ENO3	XM_011523729.2 link	c.-733_-732insC	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+190_-3+191insC	intron_variant	Intron 1 of 6	5		ENSP00000467444.1	K7EPM1
PFN1	ENST00000572383.1 link	c.77-9_77-8insG	intron_variant	Intron 1 of 2	3		ENSP00000460363.1	I3L3D5
ENO3	ENST00000519266.5 link	c.-3+216_-3+217insC	intron_variant	Intron 1 of 1	3		ENSP00000467270.1	K7EP84
PFN1	ENST00000225655.6 link	c.-170_-169insG	upstream_gene_variant		1	NM_005022.4	ENSP00000225655.5	P07737

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

7783

AN:

122194

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.0386

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0630

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0709

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0733

GnomAD3 exomes

AF:

0.0633

AC:

AN:

932

Hom.:

AF XY:

0.0611

AC XY:

AN XY:

540

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.0625

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0756

AC:

25398

AN:

336136

Hom.:

Cov.:

AF XY:

0.0781

AC XY:

13508

AN XY:

172990

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.0845

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.0568

Gnomad4 OTH exome

AF:

0.0848

GnomAD4 genome

AF:

0.0636

AC:

7776

AN:

122224

Hom.:

323

Cov.:

AF XY:

0.0649

AC XY:

3837

AN XY:

59096

show subpopulations

Gnomad4 AFR

AF:

0.0362

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0630

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0408

Gnomad4 NFE

AF:

0.0542

Gnomad4 OTH

AF:

0.0722

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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