Genetic Variant NM_001099271.2:c.513+674A>G (chr5-75701931-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001099271.2(POC5):c.513+674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,946 control chromosomes in the GnomAD database, including 13,750 homozygotes. 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: 𝑓 0.42 ( 13750 hom., cov: 31)

Consequence

POC5
NM_001099271.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.329

Publications

25 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):

scoliosis
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
ciliopathy
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

POC5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001099271.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

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.513+674A>G		intron	N/A	NP_001092741.1	Q8NA72-1
	POC5	NM_152408.3		c.438+674A>G		intron	N/A	NP_689621.2	Q8NA72-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POC5	ENST00000428202.7	TSL:1 MANE Select	c.513+674A>G	intron	N/A	ENSP00000410216.2	Q8NA72-1
POC5	ENST00000446329.6	TSL:1	c.438+674A>G	intron	N/A	ENSP00000399481.2	Q8NA72-3
POC5	ENST00000930836.1		c.633+674A>G	intron	N/A	ENSP00000600895.1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63776

AN:

151828

Hom.:

13738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.420

AC:

63827

AN:

151946

Hom.:

13750

Cov.:

AF XY:

0.425

AC XY:

31583

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.501

AC:

20770

AN:

41434

American (AMR)

AF:

0.392

AC:

5996

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1435

AN:

3470

East Asian (EAS)

AF:

0.527

AC:

2714

AN:

5152

South Asian (SAS)

AF:

0.559

AC:

2699

AN:

4824

European-Finnish (FIN)

AF:

0.388

AC:

4090

AN:

10540

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24830

AN:

67932

Other (OTH)

AF:

0.380

AC:

800

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1848

3697

5545

7394

9242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.383

Hom.:

30726

Bravo

AF:

0.418

Asia WGS

AF:

0.545

AC:

1893

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

6.6

(source)

DANN

Benign

0.61

PhyloP100

-0.33

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over