NM_005022.4:c.-78C>G

Variant names:

• chr17-4948472-G-C
• rs569094456
• NM_005022.4:c.-78C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005022.4(PFN1):​c.-78C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000011 in 1,450,104 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: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: PFN1 NM_005022.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74
• Publications: 2 publications found

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]

ENO3 Gene-Disease associations (from GenCC):

• glycogen storage disease due to muscle beta-enolase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.114860475).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFN1	NM_005022.4	MANE Select	c.-78C>G		5_prime_UTR	Exon 1 of 3	NP_005013.1	P07737
	PFN1	NM_001375991.1		c.-78C>G		5_prime_UTR	Exon 1 of 2	NP_001362920.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFN1	ENST00000225655.6	TSL:1 MANE Select	c.-78C>G		5_prime_UTR	Exon 1 of 3	ENSP00000225655.5	P07737
	PFN1	ENST00000572383.1	TSL:3	c.160C>G	p.Pro54Ala	missense	Exon 2 of 3	ENSP00000460363.1	I3L3D5
	PFN1	ENST00000929513.1		c.-78C>G		5_prime_UTR	Exon 1 of 3	ENSP00000599572.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000503 AC: 4 AN: 79522 AF XY: 0.0000223

Gnomad AFR exome AF: 0.000462

Gnomad AMR exome AF: 0.0000927

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000847 AC: 11 AN: 1297984 Hom.: 0 Cov.: 27 AF XY: 0.00000944 AC XY: 6 AN XY: 635788

African (AFR) AF: 0.00 AC: 0 AN: 26602

American (AMR) AF: 0.0000438 AC: 1 AN: 22808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19566

East Asian (EAS) AF: 0.00 AC: 0 AN: 31626

South Asian (SAS) AF: 0.0000149 AC: 1 AN: 67288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 0.00000867 AC: 9 AN: 1037672

Other (OTH) AF: 0.00 AC: 0 AN: 53752

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

African (AFR) AF: 0.0000483 AC: 2 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000438 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000269 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0083	T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.11	T
PhyloP100		3.7
MVP		0.75
GERP RS		3.1
PromoterAI		-0.12	Neutral
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

Other links and lift over

dbSNP: rs569094456; hg19: chr17-4851767;