rs192350796

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-29071387-C-A
• chr2-29071387-C-G
• chr2-29071387-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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. 13/19 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

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]

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=0.043706328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCARE	NM_001029883.3	c.2875G>T	p.Ala959Ser	missense_variant	Exon 1 of 2	ENST00000331664.6	NP_001025054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCARE	ENST00000331664.6	c.2875G>T	p.Ala959Ser	missense_variant	Exon 1 of 2	2	NM_001029883.3	ENSP00000332809.4

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

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: 0.0000126

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-29294253;