Genetic Variant CCDC61:p.Pro290Leu (chr19-46016077-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001267723.2(CCDC61):c.869C>T(p.Pro290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,234,706 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 7 hom. )

Consequence

CCDC61
NM_001267723.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.781

Publications

3 publications found

Variant links:

Genes affected

CCDC61 (HGNC:33629): (coiled-coil domain containing 61) Enables identical protein binding activity and microtubule binding activity. Involved in centriole assembly and mitotic spindle assembly. Located in centriolar satellite and ciliary basal body. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

CCDC61 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056904852).

BP6

Variant 19-46016077-C-T is Benign according to our data. Variant chr19-46016077-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 781453.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267723.2. 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
	CCDC61	NM_001267723.2	MANE Select	c.869C>T	p.Pro290Leu	missense	Exon 8 of 14	NP_001254652.1	Q9Y6R9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC61	ENST00000595358.5	TSL:5 MANE Select	c.869C>T	p.Pro290Leu	missense	Exon 8 of 14	ENSP00000471454.1	Q9Y6R9-1
CCDC61	ENST00000536603.5	TSL:1	c.552-617C>T		intron	N/A	ENSP00000444279.1	Q9Y6R9-2
CCDC61	ENST00000897318.1		c.869C>T	p.Pro290Leu	missense	Exon 8 of 14	ENSP00000567377.1

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

279

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00352

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00622

AC:

AN:

482

AF XY:

0.00654

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00915

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00333

AC:

3602

AN:

1082582

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

1648

AN XY:

511226

show subpopulations

African (AFR)

AF:

0.000567

AC:

AN:

22910

American (AMR)

AF:

0.000357

AC:

AN:

8400

Ashkenazi Jewish (ASJ)

AF:

0.0000696

AC:

AN:

14360

East Asian (EAS)

AF:

0.00

AC:

AN:

26508

South Asian (SAS)

AF:

0.0000504

AC:

AN:

19848

European-Finnish (FIN)

AF:

0.00145

AC:

AN:

21392

Middle Eastern (MID)

AF:

0.000342

AC:

AN:

2922

European-Non Finnish (NFE)

AF:

0.00376

AC:

3468

AN:

922416

Other (OTH)

AF:

0.00192

AC:

AN:

43826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

199

398

598

797

996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.00183

AC:

279

AN:

152124

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41526

American (AMR)

AF:

0.000262

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00352

AC:

239

AN:

67954

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000866

Hom.:

Bravo

AF:

0.00182

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.00076

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.58

M_CAP

Benign

0.022

MetaRNN

Benign

0.0057

MutationAssessor

Benign

0.55

PhyloP100

-0.78

PrimateAI

Uncertain

0.71

Sift4G

Benign

0.29

Vest4

0.18

MVP

0.67

MPC

0.27

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.030

gMVP

0.35

Mutation Taster

=95/5

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

Computational scores

Splicing

Publications

Other links and lift over