Genetic Variant NM_016122.3:c.408T>C (chr12-94403179-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016122.3(CEP83):c.408T>C(p.Asn136Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,523,042 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 124 hom. )

Consequence

CEP83
NM_016122.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.343

Publications

3 publications found

Variant links:

Genes affected

CEP83 (HGNC:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

CEP83 Gene-Disease associations (from GenCC):

nephronophthisis 18
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP83 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-94403179-A-G is Benign according to our data. Variant chr12-94403179-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.343 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00733 (1116/152314) while in subpopulation NFE AF = 0.0114 (777/68028). AF 95% confidence interval is 0.0108. There are 6 homozygotes in GnomAd4. There are 514 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP83	NM_016122.3	MANE Select	c.408T>C	p.Asn136Asn	synonymous	Exon 5 of 17	NP_057206.2
CEP83	NM_001042399.2		c.408T>C	p.Asn136Asn	synonymous	Exon 4 of 16	NP_001035858.1
CEP83	NM_001346457.2		c.408T>C	p.Asn136Asn	synonymous	Exon 4 of 17	NP_001333386.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP83	ENST00000397809.10	TSL:1 MANE Select	c.408T>C	p.Asn136Asn	synonymous	Exon 5 of 17	ENSP00000380911.4
CEP83	ENST00000339839.9	TSL:1	c.408T>C	p.Asn136Asn	synonymous	Exon 4 of 16	ENSP00000344655.5
CEP83	ENST00000547232.5	TSL:1	n.309T>C		non_coding_transcript_exon	Exon 5 of 17	ENSP00000447783.1

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1116

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.00340

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00869

AC:

2131

AN:

245242

AF XY:

0.00920

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00341

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0110

AC:

15109

AN:

1370728

Hom.:

124

Cov.:

AF XY:

0.0111

AC XY:

7623

AN XY:

687330

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

31454

American (AMR)

AF:

0.00521

AC:

228

AN:

43794

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

286

AN:

25588

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39122

South Asian (SAS)

AF:

0.00964

AC:

803

AN:

83288

European-Finnish (FIN)

AF:

0.00363

AC:

193

AN:

53126

Middle Eastern (MID)

AF:

0.0100

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.0125

AC:

12917

AN:

1031446

Other (OTH)

AF:

0.00986

AC:

565

AN:

57310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

626

1251

1877

2502

3128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.00733

AC:

1116

AN:

152314

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

514

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41574

American (AMR)

AF:

0.00758

AC:

116

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00849

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00340

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

777

AN:

68028

Other (OTH)

AF:

0.0114

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0104

Hom.:

Bravo

AF:

0.00801

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEP83: BP4, BS1, BS2

May 04, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nephronophthisis 18

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.3

(source)

DANN

Benign

0.49

PhyloP100

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over