rs4976691

Variant names:

• chr5-177400814-C-G
• rs4976691
• NM_001029886.3:c.-238G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-177400814-C-G
• chr5-177400814-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001029886.3(PFN3):​c.-238G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,122 control chromosomes in the GnomAD database, including 21,016 homozygotes. 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: 𝑓 0.47 (21016 hom., cov: 32)
• Consequence: PFN3 NM_001029886.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

Genes affected

PFN3 (HGNC:18627): (profilin 3) The product of this gene belongs to the profilin family of proteins. This protein binds to actin and affects the structure of the cytoskeleton. It also may be involved in spermatogenesis. It is a single exon gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFN3	NM_001029886.3	c.-238G>C		upstream_gene_variant		ENST00000358571.3	NP_001025057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFN3	ENST00000358571.3	c.-238G>C		upstream_gene_variant		6	NM_001029886.3	ENSP00000351379.2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71479 AN: 152004 Hom.: 21027 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.524

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71455 AN: 152122 Hom.: 21016 Cov.: 32 AF XY: 0.469 AC XY: 34906 AN XY: 74372

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.522

Alfa AF: 0.532 Hom.: 3023

Bravo AF: 0.442

Asia WGS AF: 0.306 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4976691; hg19: chr5-176827815;