rs377711159

Variant names:

• chr3-52149932-G-A
• rs377711159
• NM_015426.5:c.159C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_015426.5(POC1A):​c.159C>T​(p.Arg53Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,613,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: POC1A NM_015426.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.120
• 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, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-52149932-G-A is Benign according to our data. Variant chr3-52149932-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 211925.
• BP7: Synonymous conserved (PhyloP=0.12 with no splicing effect.

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.159C>T	p.Arg53Arg	synonymous	Exon 3 of 11	NP_056241.3
	POC1A	NM_001161581.2		c.45C>T	p.Arg15Arg	synonymous	Exon 3 of 11	NP_001155053.1
	POC1A	NM_001161580.2		c.159C>T	p.Arg53Arg	synonymous	Exon 3 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.159C>T	p.Arg53Arg	synonymous	Exon 3 of 11	ENSP00000296484.2
	POC1A	ENST00000394970.6	TSL:1	c.159C>T	p.Arg53Arg	synonymous	Exon 3 of 10	ENSP00000378421.2
	POC1A	ENST00000939755.1		c.159C>T	p.Arg53Arg	synonymous	Exon 3 of 11	ENSP00000609814.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000387 AC: 97 AN: 250362 AF XY: 0.000406

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000655

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000359 AC: 524 AN: 1461494 Hom.: 1 Cov.: 32 AF XY: 0.000391 AC XY: 284 AN XY: 727028

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000568 AC: 49 AN: 86258

European-Finnish (FIN) AF: 0.000207 AC: 11 AN: 53070

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.000377 AC: 419 AN: 1111970

Other (OTH) AF: 0.000480 AC: 29 AN: 60390

GnomAD4 genome AF: 0.000249 AC: 38 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20 AN XY: 74492

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.000246

EpiCase AF: 0.000654

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.9
DANN	Benign	0.71
PhyloP100		0.12
Mutation Taster		=97/3	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

dbSNP: rs377711159; hg19: chr3-52183948;