rs1065212

Positions:

• chr5-176384132-T-C

Variant summary

Our verdict is Benign. Variant got -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. 10/14 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP16	NM_016391.8	c.*99A>G		3_prime_UTR_variant	5/5	ENST00000614830.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP16	ENST00000614830.5	c.*99A>G		3_prime_UTR_variant	5/5	1	NM_016391.8	P1

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

GnomAD3 exomes AF: 0.0821 AC: 20274 AN: 246892 Hom.: 1078 AF XY: 0.0817 AC XY: 10963 AN XY: 134220

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 SAS exome AF: 0.0376

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

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0570

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0369

Gnomad4 FIN exome AF: 0.0700

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.0903

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

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0781

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0358

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0987 Hom.: 534

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.1
DANN	Benign	0.64
DEOGEN2	Benign	0.011	T;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.18	T;T;T
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.30	T;T;T
Vest4		0.046
ClinPred		0.0014	T
GERP RS		-6.0
gMVP		0.060

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

Publications

LitVar

Other links and lift over

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