Genetic Variant CEP44:p.Arg82Cys (chr4-174303709-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040157.3(CEP44):c.244C>T(p.Arg82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,521,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CEP44
NM_001040157.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Publications

2 publications found

Variant links:

Genes affected

CEP44 (HGNC:29356): (centrosomal protein 44) Enables microtubule binding activity. Involved in centriole replication and centriole-centriole cohesion. Located in centriole; centrosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

CEP44 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040157.3. 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
	CEP44	NM_001040157.3	MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 5 of 12	NP_001035247.1	Q9C0F1-1
	CEP44	NM_001145314.2		c.244C>T	p.Arg82Cys	missense	Exon 5 of 11	NP_001138786.1	Q9C0F1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP44	ENST00000503780.6	TSL:1 MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 5 of 12	ENSP00000423153.1	Q9C0F1-1
CEP44	ENST00000296519.6	TSL:1	c.244C>T	p.Arg82Cys	missense	Exon 3 of 10	ENSP00000296519.4	Q9C0F1-1
CEP44	ENST00000396791.7	TSL:1	n.244C>T		non_coding_transcript_exon	Exon 5 of 14	ENSP00000380009.3	Q9C0F1-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000122

AC:

AN:

238382

AF XY:

0.0000853

show subpopulations

Gnomad AFR exome

AF:

0.000455

Gnomad AMR exome

AF:

0.000642

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000307

AC:

AN:

1369688

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

675466

show subpopulations

African (AFR)

AF:

0.000346

AC:

AN:

31796

American (AMR)

AF:

0.000455

AC:

AN:

41778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23880

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38380

South Asian (SAS)

AF:

0.00

AC:

AN:

73870

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

51004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.00000859

AC:

AN:

1047836

Other (OTH)

AF:

0.0000179

AC:

AN:

55780

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

Exome 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

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41560

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000658

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.0048

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.0060

MutationAssessor

Pathogenic

3.1

PhyloP100

3.4

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.47

Sift

Uncertain

0.017

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.61

MVP

0.93

MPC

0.26

ClinPred

0.34

GERP RS

5.6

Varity_R

0.61

gMVP

0.83

Mutation Taster

=62/38

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.42

Position offset: -6

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