Variant 3-52096650-C-A 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 ENST00000296484.7(POC1A):c.1044G>T(p.Gln348His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,612,976 control chromosomes in the GnomAD database, including 572 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.

Frequency

Genomes: 𝑓 0.033 ( 302 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 270 hom. )

Consequence

POC1A
ENST00000296484.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.502

Variant links:

Genes affected

POC1A (HGNC:24488): (POC1 centriolar protein A) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome. [provided by RefSeq, Sep 2012]

POC1A 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=0.0014900267).

BP6

Variant 3-52096650-C-A is Benign according to our data. Variant chr3-52096650-C-A is described in ClinVar as [Benign]. Clinvar id is 129984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1A	NM_015426.5 linkuse as main transcript	c.1044G>T	p.Gln348His	missense_variant	10/11	ENST00000296484.7	NP_056241.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1A	ENST00000296484.7 linkuse as main transcript	c.1044G>T	p.Gln348His	missense_variant	10/11	1	NM_015426.5	ENSP00000296484	P1	Q8NBT0-1
POC1A	ENST00000394970.6 linkuse as main transcript	c.982-20665G>T		intron_variant		1		ENSP00000378421		Q8NBT0-2
POC1A	ENST00000474012.1 linkuse as main transcript	c.930G>T	p.Gln310His	missense_variant	10/11	2		ENSP00000418968		Q8NBT0-3

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4966

AN:

152148

Hom.:

302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00789

AC:

1969

AN:

249650

Hom.:

107

AF XY:

0.00566

AC XY:

764

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00323

AC:

4716

AN:

1460710

Hom.:

270

Cov.:

AF XY:

0.00281

AC XY:

2045

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.0327

AC:

4973

AN:

152266

Hom.:

302

Cov.:

AF XY:

0.0307

AC XY:

2286

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.0374

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.109

AC:

479

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0103

AC:

1249

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0043

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

L;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.43

N;N

REVEL

Benign

0.14

Sift

Benign

0.16

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;.

Vest4

0.19

MutPred

0.12

Gain of glycosylation at S344 (P = 0.0222);.;

MPC

0.30

ClinPred

0.0061

GERP RS

-0.24

Varity_R

0.028

gMVP

0.31

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