rs1108842

Variant names:

• chr3-52686064-A-C
• rs1108842
• NM_014366.5:c.-29A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-52686064-A-C
• chr3-52686064-A-G
• chr3-52686064-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014366.5(GNL3):​c.-29A>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014366.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL3	NM_014366.5	MANE Select	c.-29A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_055181.3
	GNL3	NM_014366.5	MANE Select	c.-29A>C		5_prime_UTR	Exon 1 of 15	NP_055181.3
	GNL3	NM_206825.2		c.-162A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_996561.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL3	ENST00000418458.6	TSL:1 MANE Select	c.-29A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000395772.1
	GNL3	ENST00000468885.1	TSL:1	n.35A>C		non_coding_transcript_exon	Exon 1 of 2
	GNL3	ENST00000418458.6	TSL:1 MANE Select	c.-29A>C		5_prime_UTR	Exon 1 of 15	ENSP00000395772.1

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

GnomAD2 exomes AF: 0.495 AC: 123108 AN: 248866 AF XY: 0.482

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 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

African (AFR) AF: 0.553 AC: 12193 AN: 22034

American (AMR) AF: 0.617 AC: 27121 AN: 43960

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 11706 AN: 22330

East Asian (EAS) AF: 0.509 AC: 18826 AN: 37002

South Asian (SAS) AF: 0.298 AC: 22103 AN: 74096

European-Finnish (FIN) AF: 0.482 AC: 25568 AN: 53076

Middle Eastern (MID) AF: 0.501 AC: 2317 AN: 4624

European-Non Finnish (NFE) AF: 0.508 AC: 280195 AN: 551582

Other (OTH) AF: 0.491 AC: 19748 AN: 40244

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

African (AFR) AF: 0.541 AC: 22416 AN: 41448

American (AMR) AF: 0.599 AC: 9158 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2350 AN: 5136

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4826

European-Finnish (FIN) AF: 0.465 AC: 4912 AN: 10574

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34475 AN: 67908

Other (OTH) AF: 0.530 AC: 1122 AN: 2116

Alfa AF: 0.511 Hom.: 82088

Bravo AF: 0.530

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.44
PhyloP100		-4.6
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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