NM_015426.5:c.*496A>G

Variant names:

• chr3-52075391-T-C
• rs747343
• NM_015426.5:c.*496A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015426.5(POC1A):​c.*496A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 155,638 control chromosomes in the GnomAD database, including 6,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6301 hom., cov: 33)
  • Exomes 𝑓: 0.21 (114 hom.)
• Consequence: POC1A NM_015426.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 11 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, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

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.*496A>G		3_prime_UTR	Exon 11 of 11	NP_056241.3
	POC1A	NM_001161581.2		c.*496A>G		3_prime_UTR	Exon 11 of 11	NP_001155053.1
	POC1A	NM_001161580.2		c.*496A>G		3_prime_UTR	Exon 10 of 10	NP_001155052.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POC1A	ENST00000296484.7	TSL:1 MANE Select	c.*496A>G		3_prime_UTR	Exon 11 of 11	ENSP00000296484.2
	POC1A	ENST00000394970.6	TSL:1	c.*496A>G		3_prime_UTR	Exon 10 of 10	ENSP00000378421.2
	POC1A	ENST00000939755.1		c.*496A>G		3_prime_UTR	Exon 11 of 11	ENSP00000609814.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39284 AN: 152002 Hom.: 6271 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.207 AC: 729 AN: 3518 Hom.: 114 Cov.: 0 AF XY: 0.206 AC XY: 378 AN XY: 1832

African (AFR) AF: 0.300 AC: 15 AN: 50

American (AMR) AF: 0.387 AC: 341 AN: 882

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2 AN: 20

East Asian (EAS) AF: 0.380 AC: 73 AN: 192

South Asian (SAS) AF: 0.145 AC: 50 AN: 344

European-Finnish (FIN) AF: 0.107 AC: 3 AN: 28

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.120 AC: 227 AN: 1886

Other (OTH) AF: 0.158 AC: 18 AN: 114

GnomAD4 genome AF: 0.259 AC: 39374 AN: 152120 Hom.: 6301 Cov.: 33 AF XY: 0.263 AC XY: 19581 AN XY: 74362

African (AFR) AF: 0.406 AC: 16825 AN: 41476

American (AMR) AF: 0.332 AC: 5073 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2410 AN: 5150

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10574

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10455 AN: 68016

Other (OTH) AF: 0.229 AC: 484 AN: 2116

Alfa AF: 0.190 Hom.: 9350

Bravo AF: 0.278

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.33
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

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: rs747343; hg19: chr3-52109407;