17-4945999-TGGA-T

Position:

• chr17-4945999-TGGA-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005022.4(PFN1):​c.326-5_326-3delTCC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000448 in 1,606,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: PFN1 NM_005022.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.75

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-4945999-TGGA-T is Benign according to our data. Variant chr17-4945999-TGGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1631283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFN1	NM_005022.4	c.326-5_326-3delTCC		splice_region_variant, intron_variant		ENST00000225655.6	NP_005013.1
PFN1	NM_001375991.1	c.*405_*407delTCC		3_prime_UTR_variant	2/2		NP_001362920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFN1	ENST00000225655.6	c.326-5_326-3delTCC		splice_region_variant, intron_variant		1	NM_005022.4	ENSP00000225655.5
PFN1	ENST00000574872.1	c.218-5_218-3delTCC		splice_region_variant, intron_variant		2		ENSP00000465019.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 151998 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.000479

GnomAD3 exomes AF: 0.0000716 AC: 18 AN: 251426 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135882

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 54 AN: 1454210 Hom.: 0 AF XY: 0.0000359 AC XY: 26 AN XY: 724020

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000262

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74352

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs759482650; hg19: chr17-4849294;