Genetic Variant CEP44:p.Ile300Val (chr4-174310795-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001040157.3(CEP44):c.898A>G(p.Ile300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,308,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CEP44
NM_001040157.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031641662).

BP6

Variant 4-174310795-A-G is Benign according to our data. Variant chr4-174310795-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3142959.Status of the report is criteria_provided_single_submitter, 1 stars.

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.898A>G	p.Ile300Val	missense	Exon 9 of 12	NP_001035247.1	Q9C0F1-1
	CEP44	NM_001145314.2		c.898A>G	p.Ile300Val	missense	Exon 9 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.898A>G	p.Ile300Val	missense	Exon 9 of 12	ENSP00000423153.1	Q9C0F1-1
CEP44	ENST00000296519.6	TSL:1	c.898A>G	p.Ile300Val	missense	Exon 7 of 10	ENSP00000296519.4	Q9C0F1-1
CEP44	ENST00000396791.7	TSL:1	n.898A>G		non_coding_transcript_exon	Exon 9 of 14	ENSP00000380009.3	Q9C0F1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.64e-7

AC:

AN:

1308202

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

657588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29150

American (AMR)

AF:

0.00

AC:

AN:

36546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24538

East Asian (EAS)

AF:

0.00

AC:

AN:

37958

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5428

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

990788

Other (OTH)

AF:

0.00

AC:

AN:

54920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.059

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0060

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.0042

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.39

M_CAP

Benign

0.0031

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.29

PhyloP100

-1.5

PrimateAI

Benign

0.27

PROVEAN

Benign

0.20

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MutPred

0.19

Gain of disorder (P = 0.0687)

MVP

0.088

MPC

0.066

ClinPred

0.028

GERP RS

-9.7

Varity_R

0.027

gMVP

0.030

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over