rs878853392

Variant names:

• chr14-21317847-A-C
• NM_020366.4:c.1303A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-21317847-A-C
• chr14-21317847-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020366.4(RPGRIP1):​c.1303A>C​(p.Lys435Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPGRIP1 NM_020366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11427748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1	NM_020366.4	c.1303A>C	p.Lys435Gln	missense_variant	Exon 11 of 25	ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7	c.1303A>C	p.Lys435Gln	missense_variant	Exon 11 of 25	1	NM_020366.4	ENSP00000382895.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451016 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720236

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.032	T;T;T;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.66	T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	.;.;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;T;D
Polyphen		0.087, 0.035	.;.;B;B;.
Vest4		0.23
MutPred		0.15		.;.;Loss of ubiquitination at K435 (P = 0.0023);.;.;
MVP		0.76
MPC		0.073
ClinPred		0.068	T
GERP RS		0.71
Varity_R		0.083
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: chr14-21786006;