rs1108842

chr3-52686064-A-Cchr3-52686064-A-Gchr3-52686064-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014366.5(GNL3):c.-29A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,000,910 control chromosomes in the GnomAD database, including 127,070 homozygotes. 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 0.52 (20522 hom., cov: 32)
  • Exomes 𝑓: 0.49 (106548 hom.)
• Consequence: GNL3 NM_014366.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNL3	NM_014366.5	c.-29A>C		5_prime_UTR_variant	1/15	ENST00000418458.6
GNL3	NM_206825.2	c.-162A>C		5_prime_UTR_variant	1/15
GNL3	NM_206826.1	c.-24+9A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNL3	ENST00000418458.6	c.-29A>C		5_prime_UTR_variant	1/15	1	NM_014366.5	P2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78287 AN: 151844 Hom.: 20503 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.526

GnomAD3 exomes AF: 0.495 AC: 123108 AN: 248866 Hom.: 31429 AF XY: 0.482 AC XY: 65005 AN XY: 134960

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.446

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.494 AC: 419777 AN: 848948 Hom.: 106548 Cov.: 12 AF XY: 0.485 AC XY: 216732 AN XY: 446734

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.516 AC: 78360 AN: 151962 Hom.: 20522 Cov.: 32 AF XY: 0.511 AC XY: 38006 AN XY: 74304

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.530

Alfa AF: 0.508 Hom.: 35112

Bravo AF: 0.530

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.20
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1108842; hg19: chr3-52720080; COSMIC: COSV66920845; COSMIC: COSV66920845;