chr12-89492071-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PM1PM2PM5BP4_ModerateBP6_Moderate

The NM_172240.3(POC1B):​c.317G>A​(p.Arg106Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,597,748 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

6
7
5

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 7.91
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a repeat WD 3 (size 38) in uniprot entity POC1B_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_172240.3
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr12-89492071-C-G is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.19926763).
BP6
Variant 12-89492071-C-T is Benign according to our data. Variant chr12-89492071-C-T is described in ClinVar as [Benign]. Clinvar id is 851405.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POC1BNM_172240.3 linkc.317G>A p.Arg106Gln missense_variant Exon 4 of 12 ENST00000313546.8 NP_758440.1 Q8TC44-1A0MNP0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POC1BENST00000313546.8 linkc.317G>A p.Arg106Gln missense_variant Exon 4 of 12 1 NM_172240.3 ENSP00000323302.3 Q8TC44-1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000269
AC:
63
AN:
234288
Hom.:
2
AF XY:
0.000221
AC XY:
28
AN XY:
126898
show subpopulations
Gnomad AFR exome
AF:
0.0000626
Gnomad AMR exome
AF:
0.000271
Gnomad ASJ exome
AF:
0.000220
Gnomad EAS exome
AF:
0.0000578
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000449
Gnomad OTH exome
AF:
0.000353
GnomAD4 exome
AF:
0.000208
AC:
301
AN:
1445448
Hom.:
1
Cov.:
30
AF XY:
0.000203
AC XY:
146
AN XY:
718742
show subpopulations
Gnomad4 AFR exome
AF:
0.0000615
Gnomad4 AMR exome
AF:
0.000275
Gnomad4 ASJ exome
AF:
0.000118
Gnomad4 EAS exome
AF:
0.0000759
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000244
Gnomad4 OTH exome
AF:
0.000201
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152300
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000365
Hom.:
0
Bravo
AF:
0.000397
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000346
AC:
42

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinal dystrophy Uncertain:1
Jan 01, 2021
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:1
Nov 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.25
T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.088
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
1.8
L;.
PROVEAN
Uncertain
-4.0
D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.90
MVP
0.84
MPC
0.40
ClinPred
0.41
T
GERP RS
5.8
Varity_R
0.71
gMVP
0.46

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

LitVar

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

Other links and lift over

dbSNP: rs76216585; hg19: chr12-89885848; COSMIC: COSV100544281; COSMIC: COSV100544281; API