Variant 3-149968534-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_053024.4(PFN2):c.149T>C(p.Met50Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000994 in 1,609,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PFN2
NM_053024.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

PFN2 (HGNC:8882): (profilin 2) The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. There are two alternatively spliced transcript variants encoding different isoforms described for this gene. [provided by RefSeq, Jul 2008]

PFN2 links:

PFN2 (HGNC:):

PFN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFN2	NM_053024.4 linkuse as main transcript	c.149T>C	p.Met50Thr	missense_variant	2/3	ENST00000239940.12	NP_444252.1	P35080-1
PFN2	NM_002628.5 linkuse as main transcript	c.149T>C	p.Met50Thr	missense_variant	2/3		NP_002619.1	P35080-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFN2	ENST00000239940.12 linkuse as main transcript	c.149T>C	p.Met50Thr	missense_variant	2/3	1	NM_053024.4	ENSP00000239940.7		P35080-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000680

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249808

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461150

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148618

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000680

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.149T>C (p.M50T) alteration is located in exon 2 (coding exon 2) of the PFN2 gene. This alteration results from a T to C substitution at nucleotide position 149, causing the methionine (M) at amino acid position 50 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.64

.;D;T;T;T;T;T;T;T;T;T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.67

T;T;.;T;.;D;T;.;.;.;.;D;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.41

N;N;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.4

N;N;.;D;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.012

D;D;.;T;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.053

T;D;.;D;D;D;T;D;D;D;D;D;T

Polyphen

0.032, 0.049, 0.030

.;B;.;B;B;B;.;.;.;.;.;.;.

Vest4

0.61

MutPred

0.41

Loss of stability (P = 0.0132);Loss of stability (P = 0.0132);.;Loss of stability (P = 0.0132);.;.;Loss of stability (P = 0.0132);.;.;.;.;.;Loss of stability (P = 0.0132);

MVP

0.41

MPC

1.3

ClinPred

0.47

GERP RS

5.4

Varity_R

0.52

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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