Variant 5-75707853-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H36C) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
POC5	NM_001099271.2 linkuse as main transcript	c.107A>G	p.His36Arg	missense_variant	3/12	ENST00000428202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC5	ENST00000428202.7 linkuse as main transcript	c.107A>G	p.His36Arg	missense_variant	3/12	1	NM_001099271.2	P1	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

GnomAD3 exomes

AF:

0.467

AC:

104883

AN:

224612

Hom.:

26233

AF XY:

0.466

AC XY:

56362

AN XY:

120902

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 SAS exome

AF:

0.570

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

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.548

AC:

83293

AN:

152072

Hom.:

25753

Cov.:

AF XY:

0.549

AC XY:

40813

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.858

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.579

Gnomad4 FIN

AF:

0.426

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.433

Hom.:

34938

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2020	This variant is associated with the following publications: (PMID: 30297969, 29632382, 28008009) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

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;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

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

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