6-13615419-G-T

Variant names:

• chr6-13615419-G-T
• rs1457258929
• NM_016167.5:c.61G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016167.5(NOL7):​c.61G>T​(p.Glu21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NOL7 NM_016167.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 0 publications found

Genes affected

NOL7 (HGNC:21040): (nucleolar protein 7) The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

ENSG00000261071 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL7	NM_016167.5	c.61G>T	p.Glu21*	stop_gained	Exon 1 of 8	ENST00000451315.7	NP_057251.2
NOL7	NM_001317724.2	c.61G>T	p.Glu21*	stop_gained	Exon 1 of 9		NP_001304653.1
LOC124901263	XR_007059461.1	n.-217C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL7	ENST00000451315.7	c.61G>T	p.Glu21*	stop_gained	Exon 1 of 8	1	NM_016167.5	ENSP00000405674.2
NOL7	ENST00000420088.1	c.-129G>T		upstream_gene_variant		2		ENSP00000404836.1
NOL7	ENST00000474485.1	n.-170G>T		upstream_gene_variant		3
ENSG00000261071	ENST00000566170.3	n.-206C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393524 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 687018

African (AFR) AF: 0.00 AC: 0 AN: 31386

American (AMR) AF: 0.00 AC: 0 AN: 35026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24968

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.00 AC: 0 AN: 78916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4780

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077346

Other (OTH) AF: 0.00 AC: 0 AN: 57694

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		0.97
Vest4		0.18
GERP RS		2.9
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=55/145	disease causing (fs/PTC)

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: rs1457258929; hg19: chr6-13615651;