Genetic Variant NOC3L:c.1470+41A>G (chr10-94344812-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_022451.11(NOC3L):c.1470+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,443,088 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0021 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 45 hom. )

Consequence

NOC3L
NM_022451.11 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

2 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00213 (324/152304) while in subpopulation EAS AF = 0.055 (285/5186). AF 95% confidence interval is 0.0497. There are 14 homozygotes in GnomAd4. There are 198 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022451.11. 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
	NOC3L	NM_022451.11	MANE Select	c.1470+41A>G		intron	N/A	NP_071896.8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOC3L	ENST00000371361.3	TSL:1 MANE Select	c.1470+41A>G	intron	N/A	ENSP00000360412.3	Q8WTT2
NOC3L	ENST00000966134.1		c.1470+41A>G	intron	N/A	ENSP00000636193.1
NOC3L	ENST00000852417.1		c.1470+41A>G	intron	N/A	ENSP00000522476.1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0552

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00504

AC:

1048

AN:

207988

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.000386

Gnomad AMR exome

AF:

0.0000862

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0622

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00182

AC:

2350

AN:

1290784

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1134

AN XY:

648068

show subpopulations

African (AFR)

AF:

0.000106

AC:

AN:

28352

American (AMR)

AF:

0.0000620

AC:

AN:

32240

Ashkenazi Jewish (ASJ)

AF:

0.0000445

AC:

AN:

22494

East Asian (EAS)

AF:

0.0504

AC:

1960

AN:

38894

South Asian (SAS)

AF:

0.000844

AC:

AN:

75808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.000188

AC:

185

AN:

984900

Other (OTH)

AF:

0.00248

AC:

135

AN:

54410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

114

229

343

458

572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.00213

AC:

324

AN:

152304

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41578

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0550

AC:

285

AN:

5186

South Asian (SAS)

AF:

0.00187

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68012

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000493

Hom.:

Bravo

AF:

0.00278

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.7

(source)

DANN

Benign

0.65

PhyloP100

0.51

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over