Variant 5-75674505-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099271.2(POC5):c.1658G>C(p.Arg553Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

POC5
NM_001099271.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

POC5 (HGNC:26658): (POC5 centriolar protein) Predicted to enable identical protein binding activity. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POC5 links:

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ANKDD1B 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=0.2566365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC5	NM_001099271.2 linkuse as main transcript	c.1658G>C	p.Arg553Thr	missense_variant	12/12	ENST00000428202.7	NP_001092741.1	Q8NA72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC5	ENST00000428202.7 linkuse as main transcript	c.1658G>C	p.Arg553Thr	missense_variant	12/12	1	NM_001099271.2	ENSP00000410216.2		Q8NA72-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.1658G>C (p.R553T) alteration is located in exon 12 (coding exon 11) of the POC5 gene. This alteration results from a G to C substitution at nucleotide position 1658, causing the arginine (R) at amino acid position 553 to be replaced by a threonine (T). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.8

M;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.5

D;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.18

MutPred

0.35

Loss of MoRF binding (P = 0.0202);.;.;.;

MVP

0.80

MPC

0.43

ClinPred

0.79

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.39

gMVP

0.49

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