Genetic Variant NM_001099271.2:c.1705C>T (chr5-75674458-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099271.2(POC5):c.1705C>T(p.His569Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H569D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

POC5
NM_001099271.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.81

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ankylosing spondylitis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANKDD1B links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2172195).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099271.2. 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
	POC5	NM_001099271.2	MANE Select	c.1705C>T	p.His569Tyr	missense	Exon 12 of 12	NP_001092741.1	Q8NA72-1
	POC5	NM_152408.3		c.1630C>T	p.His544Tyr	missense	Exon 11 of 11	NP_689621.2	Q8NA72-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POC5	ENST00000428202.7	TSL:1 MANE Select	c.1705C>T	p.His569Tyr	missense	Exon 12 of 12	ENSP00000410216.2	Q8NA72-1
POC5	ENST00000446329.6	TSL:1	c.1630C>T	p.His544Tyr	missense	Exon 11 of 11	ENSP00000399481.2	Q8NA72-3
POC5	ENST00000930836.1		c.1825C>T	p.His609Tyr	missense	Exon 13 of 13	ENSP00000600895.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111836

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

0.070

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.012

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.0

PhyloP100

7.8

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Uncertain

0.011

Sift4G

Uncertain

0.020

Polyphen

0.44

Vest4

0.13

MutPred

0.40

Gain of sheet (P = 0.0221)

MVP

0.68

MPC

0.072

ClinPred

0.62

GERP RS

5.6

Varity_R

0.080

gMVP

0.21

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over