Variant 3-52122380-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015426.5(POC1A):c.980T>C(p.Leu327Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,434,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

POC1A
NM_015426.5 missense, splice_region

Scores

Splicing: ADA: 0.0008101

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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 links:

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ACMG classification

Classification made for transcript

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 (MetaRNN=0.046832234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POC1A	NM_015426.5 linkuse as main transcript	c.980T>C	p.Leu327Pro	missense_variant, splice_region_variant	9/11	ENST00000296484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POC1A	ENST00000296484.7 linkuse as main transcript	c.980T>C	p.Leu327Pro	missense_variant, splice_region_variant	9/11	1	NM_015426.5	P1	Q8NBT0-1
POC1A	ENST00000394970.6 linkuse as main transcript	c.980T>C	p.Leu327Pro	missense_variant, splice_region_variant	9/10	1			Q8NBT0-2
POC1A	ENST00000474012.1 linkuse as main transcript	c.866T>C	p.Leu289Pro	missense_variant, splice_region_variant	9/11	2			Q8NBT0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251216

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000216

AC:

AN:

1434220

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

715294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000694

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000635

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2022

This sequence change replaces leucine with proline at codon 327 of the POC1A protein (p.Leu327Pro). There is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs539829904, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with POC1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1518740). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0052

T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.90

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.26

T;D;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.38

MutPred

0.32

Gain of relative solvent accessibility (P = 0.0483);Gain of relative solvent accessibility (P = 0.0483);.;

MVP

0.30

MPC

0.51

ClinPred

0.031

GERP RS

2.1

Varity_R

0.055

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00081

dbscSNV1_RF

Benign

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over