chr3-52096672-C-A

Variant names:

• chr3-52096672-C-A
• NM_015426.5:c.1022G>T

Variant summary

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

The NM_015426.5(POC1A):​c.1022G>T​(p.Ser341Ile) 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. 17/22 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: POC1A NM_015426.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.896
• Publications: 0 publications found

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]

POC1A Gene-Disease associations (from GenCC):

• short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

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=0.16443536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015426.5. 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
	POC1A	NM_015426.5	MANE Select	c.1022G>T	p.Ser341Ile	missense	Exon 10 of 11	NP_056241.3
	POC1A	NM_001161581.2		c.908G>T	p.Ser303Ile	missense	Exon 10 of 11	NP_001155053.1	Q8NBT0-3
	POC1A	NM_001161580.2		c.982-20687G>T		intron	N/A	NP_001155052.1	Q8NBT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1A	ENST00000296484.7	TSL:1 MANE Select	c.1022G>T	p.Ser341Ile	missense	Exon 10 of 11	ENSP00000296484.2	Q8NBT0-1
	POC1A	ENST00000394970.6	TSL:1	c.982-20687G>T		intron	N/A	ENSP00000378421.2	Q8NBT0-2
	POC1A	ENST00000939755.1		c.986G>T	p.Ser329Ile	missense	Exon 10 of 11	ENSP00000609814.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.90
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.099
Sift	Benign	0.23	T
Sift4G	Benign	0.17	T
Polyphen		0.14	B
Vest4		0.30
MutPred		0.37		Gain of glycosylation at S341 (P = 0.0024)
MVP		0.51
MPC		0.37
ClinPred		0.44	T
GERP RS		4.0
Varity_R		0.053
gMVP		0.41
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr3-52130688;