3-52686064-A-G

Variant names:

• chr3-52686064-A-G
• rs1108842
• ENST00000468885.1:n.35A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000468885.1(GNL3):​n.35A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 849,950 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: 0.0000024 (0 hom.)
• Consequence: GNL3 ENST00000468885.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60
• Publications: 98 publications found

Genes affected

GNL3 (HGNC:29931): (G protein nucleolar 3) The protein encoded by this gene may interact with p53 and may be involved in tumorigenesis. The encoded protein also appears to be important for stem cell proliferation. This protein is found in both the nucleus and nucleolus. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

PBRM1 (HGNC:30064): (polybromo 1) This locus encodes a subunit of ATP-dependent chromatin-remodeling complexes. The encoded protein has been identified as in integral component of complexes necessary for ligand-dependent transcriptional activation by nuclear hormone receptors. Mutations at this locus have been associated with primary clear cell renal cell carcinoma. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNL3	NM_014366.5	c.-29A>G		5_prime_UTR_variant	Exon 1 of 15	ENST00000418458.6	NP_055181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL3	ENST00000418458.6	c.-29A>G		5_prime_UTR_variant	Exon 1 of 15	1	NM_014366.5	ENSP00000395772.1
PBRM1	ENST00000707071.1	c.-331T>C		upstream_gene_variant				ENSP00000516722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248866 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000235 AC: 2 AN: 849950 Hom.: 0 Cov.: 12 AF XY: 0.00000447 AC XY: 2 AN XY: 447180

African (AFR) AF: 0.00 AC: 0 AN: 22062

American (AMR) AF: 0.0000227 AC: 1 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22340

East Asian (EAS) AF: 0.00 AC: 0 AN: 37008

South Asian (SAS) AF: 0.00 AC: 0 AN: 74118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 552434

Other (OTH) AF: 0.0000248 AC: 1 AN: 40284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.57
PhyloP100		-4.6
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.39		Position offset: -5
DS_DL_spliceai		0.58		Position offset: 41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1108842; hg19: chr3-52720080;