Genetic Variant POC1B:p.Ser478Asn (chr12-89421157-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_172240.3(POC1B):c.1433G>A(p.Ser478Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S478I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.370

Publications

0 publications found

Variant links:

Genes affected

POC1B (HGNC:30836): (POC1 centriolar protein B) 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. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

POC1B Gene-Disease associations (from GenCC):

cone-rod dystrophy 20
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
ciliopathy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

POC1B links:

POC1B-DUSP6 (HGNC:):

POC1B-DUSP6 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 (MetaRNN=0.055214435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POC1B	NM_172240.3	MANE Select	c.1433G>A	p.Ser478Asn	missense	Exon 12 of 12	NP_758440.1	Q8TC44-1
POC1B	NM_001199777.2		c.1307G>A	p.Ser436Asn	missense	Exon 11 of 11	NP_001186706.1	Q8TC44-2
POC1B	NM_001425771.1		c.1114-16812G>A		intron	N/A	NP_001412700.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POC1B	ENST00000313546.8	TSL:1 MANE Select	c.1433G>A	p.Ser478Asn	missense	Exon 12 of 12	ENSP00000323302.3	Q8TC44-1
POC1B	ENST00000393179.8	TSL:1	c.1043G>A	p.Ser348Asn	missense	Exon 10 of 10	ENSP00000376877.4	Q8IU52
POC1B	ENST00000549591.1	TSL:1	n.4401G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1429912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33116

American (AMR)

AF:

0.00

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25440

East Asian (EAS)

AF:

0.00

AC:

AN:

39038

South Asian (SAS)

AF:

0.00

AC:

AN:

84046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1087800

Other (OTH)

AF:

0.00

AC:

AN:

58886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.73

M_CAP

Benign

0.019

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

0.37

PROVEAN

Benign

-0.13

REVEL

Benign

0.11

Sift

Benign

0.12

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.13

MutPred

0.13

Loss of phosphorylation at S478 (P = 0.0368)

MVP

0.48

MPC

0.057

ClinPred

0.093

GERP RS

2.1

Varity_R

0.053

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over