3-52096688-G-T

Variant names:

• chr3-52096688-G-T
• rs769973716
• NM_015426.5:c.1006C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015426.5(POC1A):​c.1006C>A​(p.Pro336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POC1A NM_015426.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05809295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POC1A	NM_015426.5	c.1006C>A	p.Pro336Thr	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.1006C>A	p.Pro336Thr	missense_variant	Exon 10 of 11	1	NM_015426.5	ENSP00000296484.2
POC1A	ENST00000394970.6	c.982-20703C>A		intron_variant	Intron 9 of 9	1		ENSP00000378421.2
POC1A	ENST00000474012.1	c.892C>A	p.Pro298Thr	missense_variant	Exon 10 of 11	2		ENSP00000418968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449644 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721294

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.020
DANN	Benign	0.44
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.032
Sift	Benign	0.36	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.31		Gain of glycosylation at S341 (P = 0.0024);.;
MVP		0.048
MPC		0.35
ClinPred		0.061	T
GERP RS		-6.3
Varity_R		0.017
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs769973716; hg19: chr3-52130704;