3-52096650-C-A

Variant names:

Variant summary

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

The NM_015426.5(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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 302 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 270 hom. )

Consequence

POC1A
NM_015426.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.502

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

POC1A 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=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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015426.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POC1A	NM_015426.5	MANE Select	c.1044G>T	p.Gln348His	missense	Exon 10 of 11	NP_056241.3
POC1A	NM_001161581.2		c.930G>T	p.Gln310His	missense	Exon 10 of 11	NP_001155053.1	Q8NBT0-3
POC1A	NM_001161580.2		c.982-20665G>T		intron	N/A	NP_001155052.1	Q8NBT0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POC1A	ENST00000296484.7	TSL:1 MANE Select	c.1044G>T	p.Gln348His	missense	Exon 10 of 11	ENSP00000296484.2	Q8NBT0-1
POC1A	ENST00000394970.6	TSL:1	c.982-20665G>T		intron	N/A	ENSP00000378421.2	Q8NBT0-2
POC1A	ENST00000939755.1		c.1008G>T	p.Gln336His	missense	Exon 10 of 11	ENSP00000609814.1

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

GnomAD2 exomes

AF:

0.00789

AC:

1969

AN:

249650

AF XY:

0.00566

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 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

African (AFR)

AF:

0.119

AC:

3956

AN:

33242

American (AMR)

AF:

0.00455

AC:

203

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39558

South Asian (SAS)

AF:

0.000302

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000101

AC:

112

AN:

1111610

Other (OTH)

AF:

0.00661

AC:

399

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

193

385

578

770

963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.0327

AC:

4973

AN:

152266

Hom.:

302

Cov.:

AF XY:

0.0307

AC XY:

2286

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.115

AC:

4770

AN:

41524

American (AMR)

AF:

0.00856

AC:

131

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68030

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

218

436

653

871

1089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0127

Hom.:

194

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

PhyloP100

0.50

PrimateAI

Benign

0.31

PROVEAN

Benign

0.43

REVEL

Benign

0.14

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.0

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

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over