Variant 17-4948526-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000225655.6(PFN1):c.-132C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,026,474 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 14 hom. )

Consequence

PFN1
ENST00000225655.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.469132).

BP6

Variant 17-4948526-G-A is Benign according to our data. Variant chr17-4948526-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1179916.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 372 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFN1	NM_005022.4 linkuse as main transcript	c.-132C>T		5_prime_UTR_variant	1/3	ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1 linkuse as main transcript	c.-132C>T		5_prime_UTR_variant	1/2		NP_001362920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PFN1	ENST00000225655.6 linkuse as main transcript	c.-132C>T		5_prime_UTR_variant	1/3	1	NM_005022.4	ENSP00000225655	P1
PFN1	ENST00000572383.1 linkuse as main transcript	c.106C>T	p.Arg36Ter	stop_gained	2/3	3		ENSP00000460363
ENO3	ENST00000519266.5 linkuse as main transcript	c.-3+179G>A		intron_variant		3		ENSP00000467270
ENO3	ENST00000520221.5 linkuse as main transcript	c.-3+153G>A		intron_variant		5		ENSP00000467444

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

372

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000766

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00174

AC:

AN:

10942

Hom.:

AF XY:

0.00199

AC XY:

AN XY:

6044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0542

Gnomad NFE exome

AF:

0.000880

Gnomad OTH exome

AF:

0.00291

GnomAD4 exome

AF:

0.00128

AC:

1117

AN:

874644

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

536

AN XY:

433710

show subpopulations

Gnomad4 AFR exome

AF:

0.0000590

Gnomad4 AMR exome

AF:

0.000573

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000642

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00245

AC:

372

AN:

151830

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

271

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.000766

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.00118

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.67

MutationTaster

Benign

1.0

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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