3-52096600-T-C

Variant names:

• chr3-52096600-T-C
• NM_015426.5:c.1094A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015426.5(POC1A):​c.1094A>G​(p.His365Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POC1A NM_015426.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POC1A	NM_015426.5	c.1094A>G	p.His365Arg	missense_variant	Exon 10 of 11	ENST00000296484.7	NP_056241.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POC1A	ENST00000296484.7	c.1094A>G	p.His365Arg	missense_variant	Exon 10 of 11	1	NM_015426.5	ENSP00000296484.2
POC1A	ENST00000394970.6	c.982-20615A>G		intron_variant	Intron 9 of 9	1		ENSP00000378421.2
POC1A	ENST00000474012.1	c.980A>G	p.His327Arg	missense_variant	Exon 10 of 11	2		ENSP00000418968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1094A>G (p.H365R) alteration is located in exon 10 (coding exon 10) of the POC1A gene. This alteration results from a A to G substitution at nucleotide position 1094, causing the histidine (H) at amino acid position 365 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	0.0082	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.49
MutPred		0.31		Loss of loop (P = 0.0804);.;
MVP		0.71
MPC		1.0
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52130616;