rs1065212

Variant names:

• chr5-176384132-T-C
• rs1065212
• ENST00000618911.4:c.548A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000618911.4(NOP16):​c.548A>G​(p.Glu183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 1,611,914 control chromosomes in the GnomAD database, including 7,392 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1074 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6318 hom.)
• Consequence: NOP16 ENST00000618911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 18 publications found

Genes affected

NOP16 (HGNC:26934): (NOP16 nucleolar protein) This gene encodes a protein that is localized to the nucleolus. Expression of this gene is induced by estrogens and Myc protein and is a marker of poor patient survival in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ARL10 (HGNC:22042): (ADP ribosylation factor like GTPase 10) Predicted to enable GTP binding activity and GTPase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010706186).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000618911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP16	NM_016391.8	MANE Select	c.*99A>G		3_prime_UTR	Exon 5 of 5	NP_057475.2
	NOP16	NM_001256539.4		c.548A>G	p.Glu183Gly	missense	Exon 5 of 5	NP_001243468.2
	NOP16	NM_001256540.4		c.545A>G	p.Glu182Gly	missense	Exon 5 of 5	NP_001243469.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP16	ENST00000618911.4	TSL:1	c.548A>G	p.Glu183Gly	missense	Exon 5 of 5	ENSP00000483001.1
	NOP16	ENST00000621444.4	TSL:1	c.545A>G	p.Glu182Gly	missense	Exon 5 of 5	ENSP00000479445.1
	NOP16	ENST00000614830.5	TSL:1 MANE Select	c.*99A>G		3_prime_UTR	Exon 5 of 5	ENSP00000480832.2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16395 AN: 151850 Hom.: 1071 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.0821 AC: 20274 AN: 246892 AF XY: 0.0817

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0524

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0687

Gnomad NFE exome AF: 0.0996

Gnomad OTH exome AF: 0.0880

GnomAD4 exome AF: 0.0878 AC: 128246 AN: 1459946 Hom.: 6318 Cov.: 32 AF XY: 0.0868 AC XY: 63015 AN XY: 726368

African (AFR) AF: 0.174 AC: 5832 AN: 33474

American (AMR) AF: 0.0570 AC: 2547 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4197 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0369 AC: 3180 AN: 86240

European-Finnish (FIN) AF: 0.0700 AC: 3620 AN: 51714

Middle Eastern (MID) AF: 0.140 AC: 805 AN: 5768

European-Non Finnish (NFE) AF: 0.0923 AC: 102609 AN: 1111830

Other (OTH) AF: 0.0903 AC: 5451 AN: 60378

GnomAD4 genome AF: 0.108 AC: 16420 AN: 151968 Hom.: 1074 Cov.: 32 AF XY: 0.104 AC XY: 7745 AN XY: 74268

African (AFR) AF: 0.172 AC: 7135 AN: 41432

American (AMR) AF: 0.0781 AC: 1194 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3472

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5142

South Asian (SAS) AF: 0.0358 AC: 172 AN: 4800

European-Finnish (FIN) AF: 0.0678 AC: 717 AN: 10580

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.0921 AC: 6255 AN: 67946

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.105 Hom.: 931

Bravo AF: 0.112

TwinsUK AF: 0.0898 AC: 333

ALSPAC AF: 0.0960 AC: 370

ExAC AF: 0.0855 AC: 10347

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.1
DANN	Benign	0.64
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.50
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.30	T
Vest4		0.046
ClinPred		0.0014	T
GERP RS		-6.0
gMVP		0.060
Mutation Taster		=100/0	polymorphism (auto)

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: rs1065212; hg19: chr5-175811133; COSMIC: COSV51257427; COSMIC: COSV51257427;