POC5 p.His36Leu

Variant names:

• chr5-75707853-T-A
• rs2307111
• NM_001099271.2:c.107A>T
• POC5 p.His36Leu

Your query was ambiguous. Multiple possible variants found:

• chr5-75707853-T-A
• chr5-75707852-AT-GA
• chr5-75707852-AT-TA
• chr5-75707852-AT-CA
• chr5-75707852-ATG-TAA
• chr5-75707852-ATG-CAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099271.2(POC5):​c.107A>T​(p.His36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H36R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POC5 NM_001099271.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 114 publications found

Genes affected

POC5 (HGNC:26658): (POC5 centriolar protein) Predicted to enable identical protein binding activity. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POC5 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1496143).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099271.2. 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
	POC5	NM_001099271.2	MANE Select	c.107A>T	p.His36Leu	missense	Exon 3 of 12	NP_001092741.1	Q8NA72-1
	POC5	NM_152408.3		c.32A>T	p.His11Leu	missense	Exon 2 of 11	NP_689621.2	Q8NA72-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC5	ENST00000428202.7	TSL:1 MANE Select	c.107A>T	p.His36Leu	missense	Exon 3 of 12	ENSP00000410216.2	Q8NA72-1
	POC5	ENST00000446329.6	TSL:1	c.32A>T	p.His11Leu	missense	Exon 2 of 11	ENSP00000399481.2	Q8NA72-3
	POC5	ENST00000512125.5	TSL:1	n.310A>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152004 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224612 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434370 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 712396

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 39188

South Asian (SAS) AF: 0.00 AC: 0 AN: 82860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093854

Other (OTH) AF: 0.00 AC: 0 AN: 59404

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152004 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74210

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.021	D
Varity_R		0.22
gMVP		0.19
Mutation Taster		=296/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2307111;

hg19: chr5-75003678;