17-67721405-T-C

Variant names:

• chr17-67721405-T-C
• NM_015462.5:c.340T>C

Variant summary

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

The NM_015462.5(NOL11):​c.340T>C​(p.Ser114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NOL11 NM_015462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

Genes affected

NOL11 (HGNC:24557): (nucleolar protein 11) Enables RNA binding activity. Involved in maturation of SSU-rRNA and positive regulation of transcription of nucleolar large rRNA by RNA polymerase I. Located in nucleolus. Part of t-UTP complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288109 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL11	NM_015462.5	MANE Select	c.340T>C	p.Ser114Pro	missense	Exon 4 of 18	NP_056277.2
	NOL11	NM_001303272.2		c.-149T>C		5_prime_UTR	Exon 4 of 17	NP_001290201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL11	ENST00000253247.9	TSL:1 MANE Select	c.340T>C	p.Ser114Pro	missense	Exon 4 of 18	ENSP00000253247.4	Q9H8H0-1
	NOL11	ENST00000918421.1		c.490T>C	p.Ser164Pro	missense	Exon 4 of 18	ENSP00000588480.1
	NOL11	ENST00000918420.1		c.340T>C	p.Ser114Pro	missense	Exon 4 of 18	ENSP00000588479.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451768 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722026

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 41686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25708

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 83732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109070

Other (OTH) AF: 0.00 AC: 0 AN: 59984

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.46		Gain of sheet (P = 0.0827)
MVP		0.72
MPC		0.62
ClinPred		0.93	D
GERP RS		5.3
PromoterAI		0.030	Neutral
Varity_R		0.45
gMVP		0.81

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

hg19: chr17-65717521;