chr3-52096720-C-A

Variant names:

• chr3-52096720-C-A
• rs1365096545
• NM_015426.5:c.982-8G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015426.5(POC1A):​c.982-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000848 in 1,414,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: POC1A NM_015426.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001630
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.534
• Publications: 0 publications found

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, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-52096720-C-A is Benign according to our data. Variant chr3-52096720-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 784467.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015426.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1A	NM_015426.5	MANE Select	c.982-8G>T		splice_region intron	N/A	NP_056241.3
	POC1A	NM_001161581.2		c.868-8G>T		splice_region intron	N/A	NP_001155053.1	Q8NBT0-3
	POC1A	NM_001161580.2		c.982-20735G>T		intron	N/A	NP_001155052.1	Q8NBT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1A	ENST00000296484.7	TSL:1 MANE Select	c.982-8G>T		splice_region intron	N/A	ENSP00000296484.2	Q8NBT0-1
	POC1A	ENST00000394970.6	TSL:1	c.982-20735G>T		intron	N/A	ENSP00000378421.2	Q8NBT0-2
	POC1A	ENST00000939755.1		c.946-8G>T		splice_region intron	N/A	ENSP00000609814.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000441 AC: 9 AN: 204242 AF XY: 0.0000628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.000286

Gnomad EAS exome AF: 0.0000661

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000205

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000848 AC: 12 AN: 1414604 Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 8 AN XY: 702828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000983 AC: 3 AN: 30504

American (AMR) AF: 0.0000288 AC: 1 AN: 34670

Ashkenazi Jewish (ASJ) AF: 0.0000850 AC: 2 AN: 23520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38156

South Asian (SAS) AF: 0.0000377 AC: 3 AN: 79592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094754

Other (OTH) AF: 0.00 AC: 0 AN: 58376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.000890 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.42
PhyloP100		-0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1365096545; hg19: chr3-52130736;