4-2939572-C-G

Position:

• chr4-2939572-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291978.2(NOP14):​c.2273G>C​(p.Ser758Thr) 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 benign outcome for this variant. 14/21 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: 2.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15826279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2	c.2273G>C	p.Ser758Thr	missense_variant	16/18	ENST00000416614.7	NP_001278907.1
NOP14	NM_003703.3	c.2273G>C	p.Ser758Thr	missense_variant	16/19		NP_003694.1
NOP14	NM_001291979.2	c.2273G>C	p.Ser758Thr	missense_variant	16/17		NP_001278908.1
NOP14-AS1	NR_015453.2	n.2697+780C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7	c.2273G>C	p.Ser758Thr	missense_variant	16/18	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 09, 2021

The c.2273G>C (p.S758T) alteration is located in exon 16 (coding exon 16) of the NOP14 gene. This alteration results from a G to C substitution at nucleotide position 2273, causing the serine (S) at amino acid position 758 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0050	T;T;T;.
Eigen	Benign	-0.066
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	.;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.96	N;N;N;N
REVEL	Benign	0.052
Sift	Uncertain	0.029	D;D;D;D
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.023	B;B;B;.
Vest4		0.14
MutPred		0.34		Gain of glycosylation at T754 (P = 0.0028);Gain of glycosylation at T754 (P = 0.0028);Gain of glycosylation at T754 (P = 0.0028);Gain of glycosylation at T754 (P = 0.0028);
MVP		0.31
MPC		0.084
ClinPred		0.65	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-2941299;