dbSNP rs17517578: NOC3L:p.Ala695Thr (chr10-94338616-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022451.11(NOC3L):c.2083G>A(p.Ala695Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,552,174 control chromosomes in the GnomAD database, including 19,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.14 ( 1676 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17813 hom. )

Consequence

NOC3L
NM_022451.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Publications

19 publications found

Variant links:

Genes affected

NOC3L (HGNC:24034): (NOC3 like DNA replication regulator) Enables RNA binding activity. Predicted to be involved in DNA replication initiation. Predicted to act upstream of or within fat cell differentiation. Located in mitochondrion; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NOC3L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.010573506).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOC3L	NM_022451.11 link	c.2083G>A	p.Ala695Thr	missense_variant	Exon 18 of 21	ENST00000371361.3	NP_071896.8	Q8WTT2
NOC3L	XR_002957007.2 link	n.2184G>A		non_coding_transcript_exon_variant	Exon 18 of 22
NOC3L	XR_007061982.1 link	n.2184G>A		non_coding_transcript_exon_variant	Exon 18 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOC3L	ENST00000371361.3 link	c.2083G>A	p.Ala695Thr	missense_variant	Exon 18 of 21	1	NM_022451.11	ENSP00000360412.3		Q8WTT2

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21588

AN:

152072

Hom.:

1676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.158

GnomAD2 exomes

AF:

0.139

AC:

32759

AN:

235946

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0779

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.154

AC:

215811

AN:

1399984

Hom.:

17813

Cov.:

AF XY:

0.156

AC XY:

108118

AN XY:

693510

show subpopulations

African (AFR)

AF:

0.103

AC:

3313

AN:

32258

American (AMR)

AF:

0.0828

AC:

3299

AN:

39828

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5011

AN:

24180

East Asian (EAS)

AF:

0.00136

AC:

AN:

38950

South Asian (SAS)

AF:

0.164

AC:

12144

AN:

74186

European-Finnish (FIN)

AF:

0.160

AC:

8178

AN:

51116

Middle Eastern (MID)

AF:

0.224

AC:

1234

AN:

5514

European-Non Finnish (NFE)

AF:

0.161

AC:

173683

AN:

1076598

Other (OTH)

AF:

0.155

AC:

8896

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

8241

16482

24724

32965

41206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6200

12400

18600

24800

31000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.142

AC:

21584

AN:

152190

Hom.:

1676

Cov.:

AF XY:

0.141

AC XY:

10523

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.107

AC:

4429

AN:

41520

American (AMR)

AF:

0.120

AC:

1838

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

753

AN:

3470

East Asian (EAS)

AF:

0.00232

AC:

AN:

5178

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4820

European-Finnish (FIN)

AF:

0.151

AC:

1603

AN:

10590

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11524

AN:

68004

Other (OTH)

AF:

0.158

AC:

335

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

942

1885

2827

3770

4712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.158

Hom.:

5709

Bravo

AF:

0.134

TwinsUK

AF:

0.176

AC:

652

ALSPAC

AF:

0.151

AC:

582

ESP6500AA

AF:

0.112

AC:

493

ESP6500EA

AF:

0.160

AC:

1376

ExAC

AF:

0.138

AC:

16767

Asia WGS

AF:

0.0900

AC:

312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.4

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.47

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.025

PhyloP100

0.36

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.76

REVEL

Benign

0.066

Sift

Benign

0.39

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.030

MPC

0.071

ClinPred

0.0023

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over