17-4948472-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005022.4(PFN1):​c.-78C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000077 in 1,297,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

PFN1
NM_005022.4 5_prime_UTR

Scores

1
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23201242).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PFN1NM_005022.4 linkc.-78C>A 5_prime_UTR_variant Exon 1 of 3 ENST00000225655.6 NP_005013.1 P07737
PFN1NM_001375991.1 linkc.-78C>A 5_prime_UTR_variant Exon 1 of 2 NP_001362920.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PFN1ENST00000225655.6 linkc.-78C>A 5_prime_UTR_variant Exon 1 of 3 1 NM_005022.4 ENSP00000225655.5 P07737
PFN1ENST00000572383.1 linkc.160C>A p.Pro54Thr missense_variant Exon 2 of 3 3 ENSP00000460363.1 I3L3D5
ENO3ENST00000520221.5 linkc.-3+99G>T intron_variant Intron 1 of 6 5 ENSP00000467444.1 K7EPM1
ENO3ENST00000519266.5 linkc.-3+125G>T intron_variant Intron 1 of 1 3 ENSP00000467270.1 K7EP84

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000126
AC:
1
AN:
79522
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
44766
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000242
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000770
AC:
10
AN:
1297984
Hom.:
0
Cov.:
27
AF XY:
0.00000472
AC XY:
3
AN XY:
635788
show subpopulations
Gnomad4 AFR exome
AF:
0.0000376
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000316
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000771
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.0078
T
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.42
T
MetaRNN
Benign
0.23
T
MVP
0.74
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6

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.

Other links and lift over

dbSNP: rs569094456; hg19: chr17-4851767; API