3-52075652-C-T

Position:

• chr3-52075652-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015426.5(POC1A):​c.*235G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 395,988 control chromosomes in the GnomAD database, including 2,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1324 hom., cov: 33)
  • Exomes 𝑓: 0.079 (955 hom.)
• Consequence: POC1A NM_015426.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-52075652-C-T is Benign according to our data. Variant chr3-52075652-C-T is described in ClinVar as [Benign]. Clinvar id is 1274387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1A	NM_015426.5	c.*235G>A		3_prime_UTR_variant	11/11	ENST00000296484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1A	ENST00000296484.7	c.*235G>A		3_prime_UTR_variant	11/11	1	NM_015426.5	P1
POC1A	ENST00000394970.6	c.*235G>A		3_prime_UTR_variant	10/10	1
POC1A	ENST00000474012.1	c.*235G>A		3_prime_UTR_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17007 AN: 152056 Hom.: 1318 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0506

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0899

GnomAD4 exome AF: 0.0795 AC: 19380 AN: 243814 Hom.: 955 Cov.: 0 AF XY: 0.0784 AC XY: 10090 AN XY: 128680

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.0529

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0721

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.112 AC: 17039 AN: 152174 Hom.: 1324 Cov.: 33 AF XY: 0.113 AC XY: 8408 AN XY: 74394

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.0629

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0775 Hom.: 544

Bravo AF: 0.111

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.60

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: rs9857878; hg19: chr3-52109668;