Genetic Variant POC1A:c.*496A>G (chr3-52075391-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015426.5(POC1A):c.*496A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 155,638 control chromosomes in the GnomAD database, including 6,415 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 0.26 ( 6301 hom., cov: 33)

Exomes 𝑓: 0.21 ( 114 hom. )

Consequence

POC1A
NM_015426.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

11 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, Labcorp Genetics (formerly Invitae), Orphanet

POC1A links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POC1A	NM_015426.5 link	c.*496A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000296484.7	NP_056241.3	Q8NBT0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
POC1A	ENST00000296484.7 link	c.*496A>G	3_prime_UTR_variant	Exon 11 of 11	1	NM_015426.5	ENSP00000296484.2	Q8NBT0-1
POC1A	ENST00000394970.6 link	c.*496A>G	3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000378421.2	Q8NBT0-2
POC1A	ENST00000474012.1 link	c.*496A>G	downstream_gene_variant		2		ENSP00000418968.1	Q8NBT0-3

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39284

AN:

152002

Hom.:

6271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.207

AC:

729

AN:

3518

Hom.:

114

Cov.:

AF XY:

0.206

AC XY:

378

AN XY:

1832

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.387

AC:

341

AN:

882

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.380

AC:

AN:

192

South Asian (SAS)

AF:

0.145

AC:

AN:

344

European-Finnish (FIN)

AF:

0.107

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.120

AC:

227

AN:

1886

Other (OTH)

AF:

0.158

AC:

AN:

114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.259

AC:

39374

AN:

152120

Hom.:

6301

Cov.:

AF XY:

0.263

AC XY:

19581

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.406

AC:

16825

AN:

41476

American (AMR)

AF:

0.332

AC:

5073

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

456

AN:

3470

East Asian (EAS)

AF:

0.468

AC:

2410

AN:

5150

South Asian (SAS)

AF:

0.237

AC:

1145

AN:

4828

European-Finnish (FIN)

AF:

0.215

AC:

2275

AN:

10574

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10455

AN:

68016

Other (OTH)

AF:

0.229

AC:

484

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1382

2764

4147

5529

6911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.190

Hom.:

9350

Bravo

AF:

0.278

Asia WGS

AF:

0.388

AC:

1350

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

(source)

DANN

Benign

0.33

PhyloP100

-0.0090

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

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

Computational scores

Splicing

Publications

Other links and lift over