ENST00000568146.1:c.-25C>G

Variant names:

• chr16-67174030-C-G
• rs2233455
• ENST00000568146.1:c.-25C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000568146.1(NOL3):​c.-25C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,650 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: 0.0000021 (0 hom.)
• Consequence: NOL3 ENST00000568146.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 35 publications found

Genes affected

NOL3 (HGNC:7869): (nucleolar protein 3) This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

NOL3 Gene-Disease associations (from GenCC):

• myoclonus, familial

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonus, familial, 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL3	XM_047434851.1	c.162C>G	p.Ser54Ser	synonymous_variant	Exon 2 of 5		XP_047290807.1
NOL3	NM_001185057.3	c.-25C>G		5_prime_UTR_variant	Exon 1 of 4		NP_001171986.1
NOL3	NM_001394978.1	c.-25C>G		5_prime_UTR_variant	Exon 2 of 5		NP_001381907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL3	ENST00000564992.2	c.-8-132C>G		intron_variant	Intron 1 of 3	2		ENSP00000457720.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397650 Hom.: 0 Cov.: 33 AF XY: 0.00000290 AC XY: 2 AN XY: 689918

African (AFR) AF: 0.00 AC: 0 AN: 31790

American (AMR) AF: 0.00 AC: 0 AN: 35862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35918

South Asian (SAS) AF: 0.00 AC: 0 AN: 79868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1080080

Other (OTH) AF: 0.00 AC: 0 AN: 58084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.51
PhyloP100		-0.66
PromoterAI		-0.11	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2233455; hg19: chr16-67207933;