Genetic Variant CEP44:p.Lys256Asn (chr4-174309939-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040157.3(CEP44):c.768A>T(p.Lys256Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,460,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CEP44
NM_001040157.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00300

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11379984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP44	NM_001040157.3 link	c.768A>T	p.Lys256Asn	missense_variant	Exon 8 of 12	ENST00000503780.6	NP_001035247.1	Q9C0F1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP44	ENST00000503780.6 link	c.768A>T	p.Lys256Asn	missense_variant	Exon 8 of 12	1	NM_001040157.3	ENSP00000423153.1		Q9C0F1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250750

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460642

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.768A>T (p.K256N) alteration is located in exon 8 (coding exon 6) of the CEP44 gene. This alteration results from a A to T substitution at nucleotide position 768, causing the lysine (K) at amino acid position 256 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0048

T;.;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.61

.;.;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.38

N;N;N;N

REVEL

Benign

0.038

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.17

MutPred

0.24

Loss of ubiquitination at K256 (P = 0.0255);Loss of ubiquitination at K256 (P = 0.0255);Loss of ubiquitination at K256 (P = 0.0255);Loss of ubiquitination at K256 (P = 0.0255);

MVP

0.23

MPC

0.11

ClinPred

0.038

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.048

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over