chr4-2939339-C-G

Variant names:

• chr4-2939339-C-G
• rs145832505
• NM_001291978.2:c.2323G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001291978.2(NOP14):​c.2323G>C​(p.Glu775Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000193 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E775K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: NOP14 NM_001291978.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.52
• Publications: 3 publications found

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:20205): (NOP14 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015089184).
• BP6: Variant 4-2939339-C-G is Benign according to our data. Variant chr4-2939339-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 731089.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291978.2. 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
	NOP14	NM_001291978.2	MANE Select	c.2323G>C	p.Glu775Gln	missense	Exon 17 of 18	NP_001278907.1	P78316-1
	NOP14	NM_003703.3		c.2323G>C	p.Glu775Gln	missense	Exon 17 of 19	NP_003694.1	P78316-1
	NOP14	NM_001291979.2		c.2306+200G>C		intron	N/A	NP_001278908.1	P78316-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP14	ENST00000416614.7	TSL:1 MANE Select	c.2323G>C	p.Glu775Gln	missense	Exon 17 of 18	ENSP00000405068.2	P78316-1
	NOP14	ENST00000314262.10	TSL:1	c.2323G>C	p.Glu775Gln	missense	Exon 17 of 19	ENSP00000315674.6	P78316-1
	NOP14	ENST00000398071.4	TSL:1	c.2306+200G>C		intron	N/A	ENSP00000381146.4	P78316-2

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000223 AC: 56 AN: 251280 AF XY: 0.000155

Gnomad AFR exome AF: 0.00339

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000944 AC: 138 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.0000756 AC XY: 55 AN XY: 727134

African (AFR) AF: 0.00367 AC: 123 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.000166 AC: 10 AN: 60390

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.00107 AC XY: 80 AN XY: 74466

African (AFR) AF: 0.00402 AC: 167 AN: 41558

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.00132

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000288 AC: 35

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Uncertain	0.018	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.46
MVP		0.52
MPC		0.43
ClinPred		0.11	T
GERP RS		4.6
Varity_R		0.25
gMVP		0.34
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145832505; hg19: chr4-2941066;