chr14-24300070-C-T

Variant names:

• chr14-24300070-C-T
• rs1484675872
• NM_174913.3:c.116C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174913.3(NOP9):​c.116C>T​(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297
• Publications: 1 publications found

Genes affected

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

DHRS1 (HGNC:16445): (dehydrogenase/reductase 1) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family. The encoded enzyme contains a conserved catalytic domain and likely functions as an oxidoreductase. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08229202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174913.3. 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
	NOP9	NM_174913.3	MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 1 of 10	NP_777573.1	Q86U38-1
	NOP9	NM_001286367.2		c.116C>T	p.Pro39Leu	missense	Exon 1 of 10	NP_001273296.1	Q86U38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 1 of 10	ENSP00000267425.3	Q86U38-1
	NOP9	ENST00000396802.7	TSL:5	c.116C>T	p.Pro39Leu	missense	Exon 1 of 10	ENSP00000380020.3	Q86U38-2
	DHRS1	ENST00000860257.1		c.-219G>A		5_prime_UTR	Exon 1 of 10	ENSP00000530316.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460350 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726460

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111738

Other (OTH) AF: 0.0000166 AC: 1 AN: 60318

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.30
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.013
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.031	D
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.28		Loss of glycosylation at P39 (P = 0.0472)
MVP		0.17
MPC		0.48
ClinPred		0.18	T
GERP RS		1.5
PromoterAI		-0.066	Neutral
Varity_R		0.12
gMVP		0.33
Mutation Taster		=96/4	polymorphism

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: rs1484675872; hg19: chr14-24769276;