Variant 17-4948358-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BS2

The ENST00000225655.6(PFN1):c.37G>A(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PFN1
ENST00000225655.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

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 Uncertain_significance. Variant got 0 ACMG points.

PM1

In a chain Profilin-1 (size 138) in uniprot entity PROF1_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in ENST00000225655.6

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFN1	NM_005022.4 linkuse as main transcript	c.37G>A	p.Ala13Thr	missense_variant	1/3	ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1 linkuse as main transcript	c.37G>A	p.Ala13Thr	missense_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.37G>A	p.Ala13Thr	missense_variant	1/3	1	NM_005022.4	ENSP00000225655	P1
PFN1	ENST00000572383.1 linkuse as main transcript	c.274G>A	p.Ala92Thr	missense_variant	2/3	3		ENSP00000460363
ENO3	ENST00000520221.5 linkuse as main transcript	c.-18C>T		5_prime_UTR_variant	1/7	5		ENSP00000467444
ENO3	ENST00000519266.5 linkuse as main transcript	c.-3+11C>T		intron_variant		3		ENSP00000467270

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245708

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458170

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University

Mar 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.00032

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.4

N;.

REVEL

Uncertain

0.52

Sift

Benign

0.13

T;.

Sift4G

Benign

0.36

T;.

Polyphen

0.52

P;.

Vest4

0.27

MutPred

0.57

Loss of stability (P = 0.073);.;

MVP

0.84

MPC

1.3

ClinPred

0.45

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.56

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