chr2-29071387-C-A

Variant names:

• chr2-29071387-C-A
• rs192350796
• NM_001029883.3:c.2875G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001029883.3(PCARE):​c.2875G>T​(p.Ala959Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A959T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PCARE NM_001029883.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 0 publications found

Genes affected

PCARE (HGNC:34383): (photoreceptor cilium actin regulator) The protein encoded by this gene is highly expressed in photoreceptors and may associate with the primary cilium of the outer segment. The encoded protein appears to undergo post-translational lipid modification. Nonsense and missense variants of this gene appear to cause a recessive form of retinitis pigmentosa. [provided by RefSeq, Jun 2010]

PCARE Gene-Disease associations (from GenCC):

• PCARE-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 54

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308575 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.043706328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029883.3. 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
	PCARE	NM_001029883.3	MANE Select	c.2875G>T	p.Ala959Ser	missense	Exon 1 of 2	NP_001025054.1	A6NGG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCARE	ENST00000331664.6	TSL:2 MANE Select	c.2875G>T	p.Ala959Ser	missense	Exon 1 of 2	ENSP00000332809.4	A6NGG8
	ENSG00000308575	ENST00000835145.1		n.224+2220C>A		intron	N/A
	ENSG00000308575	ENST00000835146.1		n.207+2220C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461406 Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111908

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.16
DANN	Benign	0.85
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.68
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.010
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.0040	B
Vest4		0.057
MutPred		0.23		Gain of phosphorylation at A959 (P = 0.0505)
MVP		0.15
MPC		0.013
ClinPred		0.11	T
GERP RS		-1.3
Varity_R		0.046
gMVP		0.21
Mutation Taster		=95/5	polymorphism

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: rs192350796; hg19: chr2-29294253;