NM_001099271.2:c.1705C>G

Variant names:

• chr5-75674458-G-C
• rs1775576664
• NM_001099271.2:c.1705C>G

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.1705C>G​(p.His569Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POC5 NM_001099271.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81
• Publications: 0 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]

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ANKDD1B Gene-Disease associations (from GenCC):

• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=0.21550557).

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.1705C>G	p.His569Asp	missense	Exon 12 of 12	NP_001092741.1	Q8NA72-1
	POC5	NM_152408.3		c.1630C>G	p.His544Asp	missense	Exon 11 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.1705C>G	p.His569Asp	missense	Exon 12 of 12	ENSP00000410216.2	Q8NA72-1
	POC5	ENST00000446329.6	TSL:1	c.1630C>G	p.His544Asp	missense	Exon 11 of 11	ENSP00000399481.2	Q8NA72-3
	POC5	ENST00000930836.1		c.1825C>G	p.His609Asp	missense	Exon 13 of 13	ENSP00000600895.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.037
Eigen_PC	Benign	0.027
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.8
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.098
Sift	Benign	0.053	T
Sift4G	Benign	0.093	T
Polyphen		0.28	B
Vest4		0.29
MutPred		0.32		Loss of MoRF binding (P = 0.0491)
MVP		0.70
MPC		0.078
ClinPred		0.55	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.29
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1775576664; hg19: chr5-74970283;