rs760016635

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-4948526-G-A
• chr17-4948526-G-C
• chr17-4948526-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005022.4(PFN1):​c.-132C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,026,474 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (14 hom.)
• Consequence: PFN1 NM_005022.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02
• Publications: 0 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.469132).
• BP6: Variant 17-4948526-G-A is Benign according to our data. Variant chr17-4948526-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1179916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 372 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.-132C>T		5_prime_UTR	Exon 1 of 3	NP_005013.1	P07737
	PFN1	NM_001375991.1		c.-132C>T		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.-132C>T		5_prime_UTR	Exon 1 of 3	ENSP00000225655.5	P07737
	PFN1	ENST00000572383.1	TSL:3	c.106C>T	p.Arg36*	stop_gained	Exon 2 of 3	ENSP00000460363.1	I3L3D5
	PFN1	ENST00000929513.1		c.-132C>T		5_prime_UTR	Exon 1 of 3	ENSP00000599572.1

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 372 AN: 151720 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000766

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00174 AC: 19 AN: 10942 AF XY: 0.00199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.00128 AC: 1117 AN: 874644 Hom.: 14 Cov.: 11 AF XY: 0.00124 AC XY: 536 AN XY: 433710

African (AFR) AF: 0.0000590 AC: 1 AN: 16942

American (AMR) AF: 0.000573 AC: 6 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14610

East Asian (EAS) AF: 0.00 AC: 0 AN: 26268

South Asian (SAS) AF: 0.000642 AC: 31 AN: 48274

European-Finnish (FIN) AF: 0.0243 AC: 711 AN: 29306

Middle Eastern (MID) AF: 0.000583 AC: 2 AN: 3430

European-Non Finnish (NFE) AF: 0.000456 AC: 313 AN: 686630

Other (OTH) AF: 0.00137 AC: 53 AN: 38720

GnomAD4 genome AF: 0.00245 AC: 372 AN: 151830 Hom.: 6 Cov.: 32 AF XY: 0.00365 AC XY: 271 AN XY: 74182

African (AFR) AF: 0.0000482 AC: 2 AN: 41452

American (AMR) AF: 0.000459 AC: 7 AN: 15264

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.0291 AC: 307 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000766 AC: 52 AN: 67886

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.000344

ExAC AF: 0.00118 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.67	D
PhyloP100		2.0
GERP RS		1.6
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

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: rs760016635; hg19: chr17-4851821;