chr3-52075825-T-C

Position:

• chr3-52075825-T-C

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.*62A>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 0.203 in 1,189,084 control chromosomes in the GnomAD database, including 31,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6225 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24792 hom.)
• Consequence: POC1A NM_015426.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45

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=-0.77).
• BP6: Variant 3-52075825-T-C is Benign according to our data. Variant chr3-52075825-T-C is described in ClinVar as [Benign]. Clinvar id is 1265846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1A	NM_015426.5	c.*62A>G		3_prime_UTR_variant	11/11	ENST00000296484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1A	ENST00000296484.7	c.*62A>G		3_prime_UTR_variant	11/11	1	NM_015426.5	P1
POC1A	ENST00000394970.6	c.*62A>G		3_prime_UTR_variant	10/10	1
POC1A	ENST00000474012.1	c.*62A>G		3_prime_UTR_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39080 AN: 151970 Hom.: 6195 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.195 AC: 201877 AN: 1036996 Hom.: 24792 Cov.: 13 AF XY: 0.192 AC XY: 101835 AN XY: 531752

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.258 AC: 39171 AN: 152088 Hom.: 6225 Cov.: 32 AF XY: 0.262 AC XY: 19446 AN XY: 74340

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.230

Alfa AF: 0.182 Hom.: 3137

Bravo AF: 0.277

Asia WGS AF: 0.377 AC: 1311 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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.67
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs731684; hg19: chr3-52109841; COSMIC: COSV56590654;