5-75707853-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001099271.2(POC5):c.107A>G(p.His36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,582,712 control chromosomes in the GnomAD database, including 160,315 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H36P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.55 ( 25753 hom., cov: 32)

Exomes 𝑓: 0.42 ( 134562 hom. )

Consequence

POC5
NM_001099271.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.06

Publications

113 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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

POC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.9082254E-7).

BP6

Variant 5-75707853-T-C is Benign according to our data. Variant chr5-75707853-T-C is described in ClinVar as [Benign]. Clinvar id is 1233562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POC5	NM_001099271.2 link	c.107A>G	p.His36Arg	missense_variant	Exon 3 of 12	ENST00000428202.7	NP_001092741.1	Q8NA72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POC5	ENST00000428202.7 link	c.107A>G	p.His36Arg	missense_variant	Exon 3 of 12	1	NM_001099271.2	ENSP00000410216.2		Q8NA72-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83176

AN:

151954

Hom.:

25700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.504

GnomAD2 exomes

AF:

0.467

AC:

104883

AN:

224612

AF XY:

0.466

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.437

GnomAD4 exome

AF:

0.425

AC:

607483

AN:

1430640

Hom.:

134562

Cov.:

AF XY:

0.428

AC XY:

303932

AN XY:

710642

show subpopulations

African (AFR)

AF:

0.871

AC:

28393

AN:

32604

American (AMR)

AF:

0.404

AC:

17160

AN:

42478

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

12274

AN:

25700

East Asian (EAS)

AF:

0.563

AC:

22058

AN:

39148

South Asian (SAS)

AF:

0.567

AC:

46929

AN:

82716

European-Finnish (FIN)

AF:

0.424

AC:

22175

AN:

52348

Middle Eastern (MID)

AF:

0.481

AC:

2754

AN:

5726

European-Non Finnish (NFE)

AF:

0.393

AC:

429073

AN:

1090654

Other (OTH)

AF:

0.450

AC:

26667

AN:

59266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14900

29800

44701

59601

74501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13642

27284

40926

54568

68210

<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:

0.548

AC:

83293

AN:

152072

Hom.:

25753

Cov.:

AF XY:

0.549

AC XY:

40813

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.858

AC:

35625

AN:

41508

American (AMR)

AF:

0.466

AC:

7122

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1671

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2855

AN:

5162

South Asian (SAS)

AF:

0.579

AC:

2785

AN:

4812

European-Finnish (FIN)

AF:

0.426

AC:

4490

AN:

10542

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27145

AN:

67984

Other (OTH)

AF:

0.505

AC:

1066

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1640

3281

4921

6562

8202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.444

Hom.:

70205

Bravo

AF:

0.560

TwinsUK

AF:

0.409

AC:

1515

ALSPAC

AF:

0.392

AC:

1509

ESP6500AA

AF:

0.857

AC:

3158

ESP6500EA

AF:

0.403

AC:

3295

ExAC

AF:

0.461

AC:

55372

Asia WGS

AF:

0.594

AC:

2062

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 26, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30297969, 29632382, 28008009) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0016

T;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.085

T;T;T

MetaRNN

Benign

5.9e-7

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.7

N;.;.

PhyloP100

1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

2.7

N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.066

MPC

0.069

ClinPred

0.0072

GERP RS

5.8

Varity_R

0.064

gMVP

0.072

Mutation Taster

=296/4

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over