4-2942228-A-T

Position:

• chr4-2942228-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001291978.2(NOP14):​c.2015T>A​(p.Leu672Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOP14 NM_001291978.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0870

Genes affected

NOP14 (HGNC:16821): (NOP14 nucleolar protein) This gene encodes a protein that plays a role in pre-18s rRNA processing and small ribosomal subunit assembly. The encoded protein may be involved in the regulation of pancreatic cancer cell proliferation and migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

NOP14-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2	c.2015T>A	p.Leu672Gln	missense_variant	14/18	ENST00000416614.7	NP_001278907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7	c.2015T>A	p.Leu672Gln	missense_variant	14/18	1	NM_001291978.2	ENSP00000405068.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.2015T>A (p.L672Q) alteration is located in exon 14 (coding exon 14) of the NOP14 gene. This alteration results from a T to A substitution at nucleotide position 2015, causing the leucine (L) at amino acid position 672 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.079
DANN	Benign	0.94
DEOGEN2	Benign	0.012	T;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.40	.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;M;.;M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.046	D;D;D;D
Sift4G	Benign	0.11	T;T;D;D
Polyphen		0.38	B;B;B;.
Vest4		0.41
MutPred		0.79		Gain of glycosylation at S670 (P = 0.005);Gain of glycosylation at S670 (P = 0.005);Gain of glycosylation at S670 (P = 0.005);Gain of glycosylation at S670 (P = 0.005);
MVP		0.18
MPC		0.14
ClinPred		0.27	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-2943955;