dbSNP rs763358770: PFN4:p.Gly107Cys (chr2-24119619-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199346.3(PFN4):c.319G>T(p.Gly107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G107S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PFN4
NM_199346.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.410

Variant links:

Genes affected

PFN4 (HGNC:31103): (profilin family member 4) Predicted to enable actin monomer binding activity. Predicted to be involved in sequestering of actin monomers. Predicted to be located in cytoskeleton. Predicted to be active in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

PFN4 links:

FAM228B (HGNC:24736): (family with sequence similarity 228 member B)

FAM228B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFN4	NM_199346.3 link	c.319G>T	p.Gly107Cys	missense_variant	Exon 4 of 5	ENST00000313213.5	NP_955378.1	Q8NHR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PFN4	ENST00000313213.5 link	c.319G>T	p.Gly107Cys	missense_variant	Exon 4 of 5	1	NM_199346.3	ENSP00000322170.4	Q8NHR9
FAM228B	ENST00000613899.4 link	c.-120-15500C>A		intron_variant	Intron 3 of 10	1		ENSP00000479742.1	A0A087WVX1
PFN4	ENST00000465360.1 link	n.404G>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
FAM228B	ENST00000486967.5 link	n.123-15500C>A		intron_variant	Intron 2 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727160

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.088

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.36

Sift

Uncertain

0.015

Sift4G

Uncertain

0.052

Polyphen

0.93

Vest4

0.46

MutPred

0.46

Gain of catalytic residue at S111 (P = 0.1294);

MVP

0.77

MPC

0.28

ClinPred

0.91

GERP RS

1.2

Varity_R

0.30

gMVP

0.64

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over