14-21294785-G-C

Variant names:

• chr14-21294785-G-C
• NM_020366.4:c.194G>C

Variant summary

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

The NM_020366.4(RPGRIP1):​c.194G>C​(p.Trp65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPGRIP1 NM_020366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1	NM_020366.4	c.194G>C	p.Trp65Ser	missense_variant	Exon 3 of 25	ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7	c.194G>C	p.Trp65Ser	missense_variant	Exon 3 of 25	1	NM_020366.4	ENSP00000382895.2
RPGRIP1	ENST00000557771.5	c.194G>C	p.Trp65Ser	missense_variant	Exon 2 of 24	5		ENSP00000451219.1
RPGRIP1	ENST00000556336.5	c.194G>C	p.Trp65Ser	missense_variant	Exon 2 of 21	5		ENSP00000450445.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1443720 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 718062

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: 0.00000273

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.046	T;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.98	.;.;D
Vest4		0.57
MutPred		0.33		Loss of catalytic residue at L63 (P = 0.012);Loss of catalytic residue at L63 (P = 0.012);Loss of catalytic residue at L63 (P = 0.012);
MVP		0.87
MPC		0.47
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.21
gMVP		0.19

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: chr14-21762944;