rs377711159

chr3-52149932-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_015426.5(POC1A):c.159C>T(p.Arg53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,613,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: POC1A NM_015426.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.120

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-52149932-G-A is Benign according to our data. Variant chr3-52149932-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211925.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=0.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1A	NM_015426.5	c.159C>T	p.Arg53=	synonymous_variant	3/11	ENST00000296484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1A	ENST00000296484.7	c.159C>T	p.Arg53=	synonymous_variant	3/11	1	NM_015426.5	P1
POC1A	ENST00000394970.6	c.159C>T	p.Arg53=	synonymous_variant	3/10	1
POC1A	ENST00000474012.1	c.45C>T	p.Arg15=	synonymous_variant	3/11	2

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000387 AC: 97 AN: 250362 Hom.: 0 AF XY: 0.000406 AC XY: 55 AN XY: 135460

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000655

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000359 AC: 524 AN: 1461494 Hom.: 1 Cov.: 32 AF XY: 0.000391 AC XY: 284 AN XY: 727028

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000568

Gnomad4 FIN exome AF: 0.000207

Gnomad4 NFE exome AF: 0.000377

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000249 AC: 38 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20 AN XY: 74492

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.000246

EpiCase AF: 0.000654

EpiControl AF: 0.000474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	POC1A: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Sep 11, 2023	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 16, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	6.9
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377711159; hg19: chr3-52183948;