rs747343

Positions:

• chr3-52075391-T-C
• chr3-52075391-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POC1A	NM_015426.5	c.*496A>G		3_prime_UTR_variant	11/11	ENST00000296484.7	NP_056241.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1A	ENST00000296484	c.*496A>G		3_prime_UTR_variant	11/11	1	NM_015426.5	ENSP00000296484.2
POC1A	ENST00000394970	c.*496A>G		3_prime_UTR_variant	10/10	1		ENSP00000378421.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39284 AN: 152002 Hom.: 6271 Cov.: 33

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.: 0 AF XY: 0.206 AC XY: 378 AN XY: 1832

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.259 AC: 39374 AN: 152120 Hom.: 6301 Cov.: 33 AF XY: 0.263 AC XY: 19581 AN XY: 74362

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.229

Alfa AF: 0.165 Hom.: 4091

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
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs747343; hg19: chr3-52109407;