17-4948526-G-T

Variant names:

• chr17-4948526-G-T
• rs760016635
• NM_005022.4:c.-132C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005022.4(PFN1):​c.-132C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 874,652 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: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PFN1 NM_005022.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFN1	NM_005022.4	c.-132C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1	c.-132C>A		5_prime_UTR_variant	Exon 1 of 2		NP_001362920.1
ENO3	XM_011523729.2	c.-770G>T		upstream_gene_variant			XP_011522031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFN1	ENST00000225655.6	c.-132C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_005022.4	ENSP00000225655.5
PFN1	ENST00000572383.1	c.106C>A	p.Arg36Arg	synonymous_variant	Exon 2 of 3	3		ENSP00000460363.1
ENO3	ENST00000520221.5	c.-3+153G>T		intron_variant	Intron 1 of 6	5		ENSP00000467444.1
ENO3	ENST00000519266.5	c.-3+179G>T		intron_variant	Intron 1 of 1	3		ENSP00000467270.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 874652 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 433718

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: 0.00000146

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs760016635; hg19: chr17-4851821;