Genetic Variant POC1A:c.982-8G>A (chr3-52096720-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015426.5(POC1A):c.982-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,644 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

POC1A
NM_015426.5 splice_region, intron

Scores

Splicing: ADA: 0.00008902

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.534

Publications

0 publications found

Variant links:

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)

POC1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414644

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702842

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

30514

American (AMR)

AF:

0.00

AC:

AN:

34690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23522

East Asian (EAS)

AF:

0.00

AC:

AN:

38156

South Asian (SAS)

AF:

0.00

AC:

AN:

79592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1094760

Other (OTH)

AF:

0.00

AC:

AN:

58378

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.2

(source)

DANN

Benign

0.35

PhyloP100

-0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000089

dbscSNV1_RF

Benign

0.018

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over